Urea compound and use thereof

Abstract

The present invention relates to a urea compound and use thereof and, more specifically, to a urea compound, or a pharmaceutically acceptable salt or stereoisomer thereof, and use thereof as an activator of beta-glucocerebrosidase.

Description

TITLE OF INVENTION UREA COMPOUND AND USE THEREOF TECHNICAL FIELD The present invention relates to a urea compound and a use thereof, and more particularly, to a urea compound, or a pharmaceutically acceptable salt or stereoisomer thereof, and a use thereof as an activator of p-glucocerebrosidase. BACKGROUND ART Mutations in p-glucocerebrosidase (GCase, gene code: GBA1) have been reported to be associated with an increased risk of developing Parkinson's disease (PD). The disease pattern varies depending on the type of p-glucocerebrosidase mutation: autosomal recessive (homozygous) mutations cause Gaucher's disease, which is known as a lysosomal storage disease, and autosomal single-allele (heterozygous) mutations were previously considered not to be associated with pathological processes. However, Studies have shown that the presence of a p-glucocerebrosidase mutation (whether homozygous or heterozygous) increases the risk of Parkinson's disease by about a 5.43-6.48-fold increase (Sidransky et al, 2009, N. Engl. J. Med.). As a result of studies, it has been known that 5-10% of Parkinson's disease patients have a p-glucocerebrosidase mutation, and that this proportion may be higher in the Ashkenazi Jewish population. Parkinson's disease caused by p-glucocerebrosidase mutations is clinically difficult to distinguish from typical Parkinson's disease, but generally has a slightly earlier age of onset (~5 years) and a higher frequency of cognitive impairment. The pathological and imaging features and the response to drug treatment are the same as those of typical Parkinson's disease. p-glucocerebrosidase mutations cause a decrease in enzyme activity and the trapping of the mutant protein in the endoplasmic reticulum (ER), which induces protein aggregation reactions and ER-associated degradation and stress. Both of these mechanisms are important in the pathogenesis of Gaucher's disease and Parkinson's disease and lead to lysosomal dysfunction. In the brains of patients with Parkinson's disease with p-glucocerebrosidase mutations, a decrease in the activity of the p-glucocerebrosidase enzyme and an increase in a-synuclein have been reported, and conversely, in the brains of typical Parkinson's disease, it has also been reported that a-synuclein is accumulated and the activity of the P—glucocerebrosidase enzyme is lowered. In addition, p-glucocerebrosidase mutations are also associated with an increased risk of Lewy body dementia and other synucleinopathies (Schapira, 2015, Mol.Cell Neurosci.). DISCLOSURE OF INVENTION TECHNICAL PROBLEM The present invention aims to prevent, alleviate or treat diseases such as Parkinson's disease, Gaucher's disease and Lewy body dementia, and other synucleinopathies, by increasing the activity of P-glucocerebrosidase to reduce the level of a-synuclein. An object of the present invention is to provide a derivative compound comprising pyridine urea or pyrimidine urea, or a pharmaceutically acceptable salt or stereoisomer thereof, as an activator of P-glucocerebrosidase. In addition, another object of the present invention is to provide a pharmaceutical composition comprising the above derivative compound comprising pyridine urea or pyrimidine urea, or a pharmaceutically acceptable salt or stereoisomer thereof, as an active ingredient. SOLUTION TO PROBLEM In order to solve the above technical problems, the present invention provides a compound of the following Formula 1, or a pharmaceutically acceptable salt or stereoisomer thereof: [Formula 1] wherein, in Formula 1, X is N or CH; R1 and R3 are each independently -H, halo, alkyl or wherein R is , and m is 1 or 2; wherein R8 is -H, alkyl, hydroxyalkyl, haloalkyl, dialkylaminocarbonyloxyalkyl or aryl; R2 is -H, halo or alkyl; R4 is -H or alkyl; R5 is -H, alkyl or cycloalkyl; R6 is saturated or partially unsaturated carbocyclyl, aryl or partially unsaturated heterocyclyl; wherein the saturated or partially unsaturated carbocyclyl and aryl may be optionally substituted with one or more substituents selected from the group consisting of halo, alkyl, hydroxyalkyl, haloalkyl, haloalkoxy, cycloalkyl and alkoxycarbonylalkyl; n is 0 or 1; and the partially unsaturated heterocyclyl may contain one or more heteroatoms selected from N, O and S, provided that at least one of R1 and R3 is Throughout the present specification, in defining the compound of Formula 1, the following concepts defined for substituents are used unless otherwise stated. As used herein, the term “hydroxy” group means -OH. As used herein, the term “halo”, when used alone or in combination with other additional terms (for example, haloalkyl), represents a radical that is fluorine (F), chlorine (Cl), bromine (Br) or iodine (I). As used herein, the term “carbonyl” group means -C(=O)-. As used herein, the term “alkyl”, when used alone or in combination with other additional terms (for example, haloalkyl), means a radical of a straight-chain or branched saturated aliphatic hydrocarbon group having, for example, 1 to or 1 to 5 carbon atoms. Examples of typical alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl and 1,2-dimethylpropyl, and the like. As used herein, the term “cycloalkyl” means a radical of a cyclic saturated aliphatic hydrocarbon group having, for example, 3 to 10 or 3 to 8 carbon atoms. Examples of typical cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. As used herein, the term “alkoxy” means alkyloxy (an -O-alkyl group), for example, alkyloxy having 1 to 7 or 1 to 5 carbon atoms. As used herein, the term “aryl” means an aromatic hydrocarbon having, for example, 6 to 10 carbon atoms, and specific examples thereof include, but are not limited to, phenyl and naphthyl. As used herein, the term “saturated or partially unsaturated carbocyclyl” means a radical of a saturated or partially unsaturated hydrocarbon forming a single or fused ring having, for example, 5 to 12 or 6 to 12 carbon atoms. The saturated or partially unsaturated carbocyclyl may include a bridged structure, a fused structure or a spiro structure. As used herein, the term “partially unsaturated heterocyclyl” means a cyclic, for example, 5- to 12-membered or 8- to 12-membered, partially unsaturated hydrocarbon comprising one or more heteroatoms selected from N, O and S as ring atoms. The compound of Formula 1 according to the present invention may form a pharmaceutically acceptable salt. The pharmaceutically acceptable salt includes all of acid or base addition salts and stereochemically isomeric forms thereof. The salt includes, without particular limitation, any salt that maintains the activity of the parent compound in a subject to be administered and does not cause undesirable effects. Such salts include inorganic salts and organic salts, and may be, for example, acetic acid, nitric acid, aspartic acid, sulfonic acid, sulfuric acid, maleic acid, glutamic acid, formic acid, succinic acid, phosphoric acid, phthalic acid, tannic acid, tartaric acid, hydrobromic acid, propionic acid, benzenesulfonic acid, benzoic acid, stearic acid, esylic acid, lactic acid, bicarbonic acid, bisulfuric acid, bitartaric acid, oxalic acid, butyric acid, calcium edetic acid, camsylic acid, carbonic acid, chlorobenzoic acid, citric acid, edetic acid, toluenesulfonic acid, edisylic acid, fumaric acid, gluceptic acid, pamoic acid, gluconic acid, glycollylarsanilic acid, methylnitric acid, polygalacturonic acid, hexylresorcinoic acid, malonic acid, hydrabamic acid, hydrochloric acid, hydroiodic acid, hydroxynaphthoic acid, isethionic acid, lactobionic acid, mandelic acid, estolic acid, mucic acid, napsylic acid, muconic acid, p-nitromethanesulfonic acid, hexamic acid, pantothenic acid, monohydrogen phosphoric acid, dihydrogen phosphoric acid, salicylic acid, sulfamic acid, sulfanilic acid, methanesulfonic acid, camphorsulfonic acid or teoclic acid. In addition, the forms of the basic salt include, for example, alkali and alkaline earth metal salts such as ammonium salts, lithium salts, sodium salts, potassium salts, magnesium salts and calcium salts, salts with organic bases such as, for example, benzathine, N-methyl-D-glucamine and hydrabamine salts, and salts with amino acids such as, for example, arginine and lysine. In addition, the salt form may also be converted into a free form by treatment with an appropriate base or acid. The term "addition salt" includes solvates that the compound of Formula 1 and salts thereof can form. Such solvates are, for example, hydrates and alcoholates. According to one embodiment of the present invention, the pharmaceutically acceptable salt may be nitrate, sulfate, hydrobromide, toluenesulfonate, hydrochloride, methanesulfonate or camphorsulfonate. Since the compounds according to the present invention may have an asymmetric carbon center and an asymmetric axis or asymmetric plane, they may exist as all optical isomers and stereoisomers, including substantially pure enantiomers such as R and S enantiomers as well as mixture racemates, and all of these isomers and mixtures are included within the scope of the present invention. With respect to pure enantiomers, the optical purity of the enantiomer may be preferably 60%ee or more, more preferably 95%ee or more, and most preferably 98%ee or more. When the compound of Formula 1 according to the present invention is a racemate, the racemate may be separated into the respective isomers by a conventional separation method, for example, by normal-phase or reverse-phase chiral column chromatography using a corresponding developing solvent, preferably by mixing  hexane, ethyl acetate, dichloromethane, methanol, etc. in the normal phase, or by mixing water and acetonitrile, etc. in the reverse phase. According to another embodiment of the present invention X is N or CH; R1 and R3 are each independently -H, halo, C1-C alkyl or , in Formula 1, ; wherein R is or , and m is 1 or 2; wherein R8 is -H, C1-C alkyl, hydroxy- C1-C alkyl, halo-C1-C alkyl, di(C1-C alkyl)aminocarbonyloxy-C1-C alkyl or C6-C10 aryl; R2 is -H, halo or C1-C alkyl; R4 is -H or C1-C alkyl; R5 is -H, C1-C alkyl or C3-C10 cycloalkyl; R6 is saturated or partially unsaturated C5-C12 carbocyclyl, C6-C10 aryl or partially unsaturated 5- to 12-membered heterocyclyl; wherein the saturated or partially unsaturated carbocyclyl and aryl may be optionally substituted with 1 to 3 substituents selected from the group consisting of halo, C1-C alkyl, hydroxy-C1-C alkyl, halo-C1-C alkyl, halo-C1-C alkoxy, C3-C10 cycloalkyl and C1-C alkoxycarbonyl-C1-C alkyl; n is 0 or 1; and the partially unsaturated heterocyclyl may contain 1 to 3 heteroatoms selected from N, O and S, provided that at least one of R1 and R3 is According to another embodiment of the present invention, in Formula 1, R1 is -H or ; wherein R is or , and m is 1 or 2; wherein R8 is -H, C1-C5 alkyl, hydroxy-C1-C5 alkyl, halo-C1-C5 alkyl, di(C1-C5 alkyl)aminocarbonyloxy-C1-C5 alkyl or phenyl; and R3 is -H, C1-C5 alkyl or wherein R is or , and m is 1 or 2; wherein R8 is -H or C1-C5 alkyl, provided that at least one of R1 and R3 is According to another embodiment of the present invention, in Formula 1, R2 is -H, halo or C1-C5 alkyl. According to another embodiment of the present invention, in Formula 1, R4 is -H or C1-C5 alkyl. According to another embodiment of the present invention, in Formula 1, R5 is -H, C1-C5 alkyl or C3-C8 cycloalkyl. According to another embodiment of the present invention, in Formula 1, R6 is saturated or partially unsaturated C6-C12 carbocyclyl, phenyl or partially unsaturated 8- to 12membered heterocyclyl, wherein the saturated or partially unsaturated carbocyclyl may be optionally substituted with 1 to 3 substituents selected from the group consisting of halo, C1-C alkyl, hydroxy-C1-C alkyl, halo-C1-C alkyl and C1-C alkoxycarbonyl-C1-C alkyl; and the phenyl may be optionally substituted with 1 to 3 substituents selected from the group consisting of halo, C1-C alkyl, halo-C1-C alkyl, halo-C1-C alkoxy and C3-C10 cycloalkyl. According to another embodiment of the present invention, in Formula 1, R6 is saturated or partially unsaturated C6-C12 carbocyclyl, or partially unsaturated 8- to 12membered heterocyclyl, wherein the saturated or partially unsaturated carbocyclyl may be optionally substituted with 1 to 3 substituents selected from the group consisting of halo, C1-C alkyl, hydroxy-C1-C alkyl, halo-C1-C alkyl and C1-C alkoxycarbonyl-C1-C alkyl. According to another embodiment of the present invention, the saturated or partially unsaturated C6-C12 carbocyclyl, or partially unsaturated 8- to 12-membered heterocyclyl of R6 may be cyclohexyl, spiro[2.5]octyl, spiro[3.5]nonyl, adamantyl, norbornanyl, indanyl, tetralinyl or chromanyl. In another embodiment according to the present invention, representative examples of the compound of Formula 1 include, but are not limited to, the compounds listed below. 1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 1); 1-[(2-{1-ethyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 2); 1-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 3); 2-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 4); 2-[(2-{1-methyl-3-[(1s,4s)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 5); 1-({2-[3-(4,4-difluorocyclohexyl)-1-methylureido]-4-pyridyl}methyl)-1H-tetrazole (Compound 6); 2-[(2-{1-methyl-3-[(1r,4r)-4-(trifluoromethyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound ); 2-[(2-{1-methyl-3-[(1r,4r)-4-isopropylcyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 8); 1-[(2-{1-methyl-3-(6-spiro[2.5]octyl)ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 9); 1-[(2-{1-methyl-3-( -spiro[3.5]nonyl)ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 10); 1-methyl-3-[(4-methylcyclohexyl)methyl]-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 11); 2-[(2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 14); 1-[(2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 15); 5-methyl-2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 16); 5-methyl-1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 1 ); 2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-propyl-2H-tetrazole (Compound 18); 1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5- propyl-1H-tetrazole (Compound 19); 2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-(trifluoromethyl)-2H-tetrazole (Compound 20); 1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-(trifluoromethyl)-1H-tetrazole (Compound 21); 2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 22); {1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazol-5-yl}methanol (Compound 23); {2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazol-5-yl}methanol (Compound 24); [2-({2-[methyl({[(1r,4r)-4-tert-butylcyclohexyl]carbamoyl})amino]pyridin-4-yl}methyl)-2H-1,2,3,4-tetrazol-5-yl]methyl N,N-dimethylcarbamate (Compound 25); 1-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 26); 2-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4- pyridyl)methyl]-2H-tetrazole (Compound 2 ); 2-[(5-fluoro-2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 28); 1-[(5-fluoro-2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 29); 1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-1H-tetrazole (Compound 45); 2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole (Compound 46); 1-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-1H-tetrazole (Compound 4 ); 2-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole (Compound 48); 1-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-1H-tetrazole (Compound 49); 2-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole (Compound 50); 1-({2-[3-(4,4-dimethylcyclohexyl)-1-methylureido]-4-pyridyl}methyl)-1H-tetrazole (Compound 51); 3-[(1R)-1-cyclohexylethyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 58); 3-[(1,4-dimethylcyclohexyl)methyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 59); 2-[(1r,4r)-4-(3-methyl-3-{4-[(2H-tetrazol-2-yl)methyl]-2-pyridyl}ureido)cyclohexyl]-2-propanol (Compound 60); 2-[(2-{1-methyl-3-[(1r,4r)-4-(1-fluoro-1-methylethyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 61); 1-[(6-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-2-pyridyl)methyl]-1H-tetrazole (Compound 6 ); 2-[(6-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-2-pyridyl)methyl]-2H-tetrazole (Compound 68); 1-(1-adamantyl)-3-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 69); 1-(1-adamantyl)-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 0); 3-methyl-1-[(1r,4r)-4-tert-butylcyclohexyl]-3-{4-[2-(2H-1,2,3,4-tetrazol-2-yl)ethyl]pyridin-2-yl}urea (Compound 1); 3-methyl-1-[(1r,4r)-4-tert-butylcyclohexyl]-3-{4-[2-(1H-1,2,3,4-tetrazol-1-yl)ethyl]pyridin-2-yl}urea (Compound 2); methyl                                             2-[1-[[[4-(tetrazol-2-ylmethyl)-2- pyridyl]carbamoylamino]methyl]cyclohexyl]acetate (Compound 3); 1-[(2R,4R)-norbornan-2-yl]-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 4); and 1-[1-(1-adamantyl)ethyl]-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 5). In another embodiment according to the present invention, representative examples of the compound of Formula 1 include, but are not limited to, the compounds listed below. 3-(4-cyclopropylphenyl)-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 12); 1-methyl-3-(4-propylphenyl)-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 13); 1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 30); 1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 31); 1-[4-[(5-methyltetrazol-1-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 32); 1-[4-[(5-methyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 33); 1-[4-[[5-(hydroxymethyl)tetrazol-1-yl]methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 34); 1-[4-[[5-(hydroxymethyl)tetrazol-2-yl]methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 35); 1-[6-methyl-4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 36); 1-[6-methyl-4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 3 ); 1-[6-methyl-4-[(5-methyltetrazol-1-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 38); 1-[6-methyl-4-[(5-methyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 39); 1-[4-[[5-(hydroxymethyl)tetrazol-1-yl]methyl]-6-methyl-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 40); 1-[4-[[5-(hydroxymethyl)tetrazol-2-yl]methyl]-6-methyl-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 41); 1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 42); 1-methyl-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 43); 1-[4-[(5-phenyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 44); 3-[cyclopropyl(phenyl)methyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 52); 3-[(R)-cyclopropyl-(2-fluorophenyl)methyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 53); 3-[(R)-cyclopropyl-(2-fluorophenyl)methyl]-1-methyl-1-[4-(tetrazol-2-ylmethyl)-2- pyridyl]urea (Compound 62); 1-ethyl-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 65); and 1-(4-isopropylphenyl)-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 66). In another embodiment according to the present invention, representative examples of the compound of Formula 1 include, but are not limited to, the compounds listed below. 3-indan-2-yl-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 54); 3-indan-1-yl-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 55); 1-methyl-3-tetralin-1-yl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 56); 3-(2,2-dimethylchroman-4-yl)-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 5 ); 1-methyl-3-[(1S)-tetralin-1-yl]-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 63); and 1-methyl-3-[(1R)-tetralin-1-yl]-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 64). According to another aspect of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of a disease mediated by P-glucocerebrosidase, comprising, as an active ingredient, the compound of Formula 1, or a pharmaceutically acceptable salt or stereoisomer thereof, together with a pharmaceutically acceptable carrier. In the present specification, “prevention” means reducing the likelihood of contracting a disease or eliminating the likelihood. In the present specification, “treatment” means, when used in a subject showing symptoms of onset, stopping, delaying or alleviating the progression of a disease. In the present specification, a "pharmaceutical composition" may comprise, in addition to the active compound according to the present invention, other chemical components such as a carrier, a diluent, an excipient, and the like. Accordingly, the pharmaceutical composition may comprise, as needed, a pharmaceutically acceptable carrier, diluent, excipient, or a combination thereof. Such a pharmaceutical composition facilitates the administration of the active compound into an organism. Various techniques for administering a pharmaceutical composition comprising a compound are known, including, but not limited to, oral, injection, aerosol, parenteral, and topical administration, and the like. In addition, the pharmaceutical composition may be sterilized, may further comprise adjuvants such as preservatives, stabilizers, wetting agents or emulsification promoters, salts for osmotic pressure control and / or buffers, may further comprise other therapeutically useful substances, and may be formulated according to conventional methods of mixing, granulation or coating. In the present specification, a “carrier” means a compound that facilitates the introduction of a compound into cells or tissues. For example, dimethyl sulfoxide (DMSO) is a common carrier that facilitates the introduction of many organic compounds into cells or tissues of an organism. In the present specification, a “diluent” is defined as a compound that not only stabilizes the biologically active form of a target compound but is also diluted in water that dissolves the compound. Salts dissolved in a buffer solution are used as diluents in the art. A commonly used buffer solution is phosphate-buffered saline, which mimics the salt form of human solutions. Since buffer salts can control the pH of a solution at low concentrations, a buffered diluent rarely modifies the biological activity of a compound. In the present specification, “pharmaceutically acceptable” means a property that does not impair the biological activity and physical properties of a compound. In another embodiment according to the present invention, the disease mediated by 0-glucocerebrosidase may be Parkinson's disease, Gaucher’s disease, Lewy body dementia or synucleinopathy, and may include any disease known to be associated with the activity of 0-glucocerebrosidase. In another embodiment according to the present invention, whether 0-glucocerebrosidase activity is increased may be measured using a wild-type or 0-glucocerebrosidase variant animal model or an animal model overexpressing the accumulation of synuclein. The pharmaceutical composition may be formulated into various oral dosage forms or parenteral dosage forms. For example, it may be in any formulation for oral administration, such as tablets, pills, hard and soft capsules, solutions, suspensions, emulsions, syrups, granules, elixirs, and the like. Such formulations for oral administration may comprise, in addition to the effective ingredient, according to the conventional composition of each formulation, a pharmaceutically acceptable carrier, for example, a diluent such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine, or a lubricant such as silica, talc, stearic acid and its magnesium or calcium salt and / or polyethylene glycol. In addition, when the formulation for oral administration is a tablet, it may comprise a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, and, in some cases, may further comprise a disintegrant such as starch, agar, alginic acid or its sodium salt, an effervescent mixture and / or an absorbent, a colorant, a flavoring agent or a sweetener, and the like. The pharmaceutical composition may also be formulated into a parenteral dosage form, in which case it is administered by a parenteral administration method such as subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection. Here, in order to formulate it into a formulation for parenteral administration, the pharmaceutical composition may be prepared as a solution or suspension by mixing the active ingredient, that is, the compound of Formula 1, or a pharmaceutically acceptable salt or stereoisomer thereof, with a stabilizer or buffer in water, and such a solution or suspension may be prepared in a unit dosage form of an ampoule or vial. In addition, the pharmaceutical composition may be sterilized, may further comprise adjuvants such as preservatives, stabilizers, wetting agents or emulsification promoters, salts for osmotic pressure control and / or buffers, may further comprise other therapeutically useful substances, and may be formulated according to conventional methods of mixing, granulation or coating. The active ingredient, that is, the compound of Formula 1, or a pharmaceutically acceptable salt or stereoisomer thereof, may be included in the pharmaceutical composition in an effective amount of, for example, 0.1 to 1,000 mg / kg (body weight) per day for mammals including humans. EFFECTS OF INVENTION According to the present invention, a novel pyridine urea or pyrimidine urea derivative compound exhibiting an excellent activator effect on P-glucocerebrosidase, or a pharmaceutically acceptable salt or stereoisomer thereof, may be provided. The pyridine urea or pyrimidine urea derivative compound, or a pharmaceutically acceptable salt or stereoisomer thereof, according to the present invention may be effectively used for the prevention or treatment of diseases mediated by P-glucocerebrosidase, for example, diseases such as Parkinson's disease, Gaucher's disease and Lewy body dementia, and other synucleinopathies. In addition, according to the present invention, a method for preparing the pyridine urea or pyrimidine urea derivative compound, a pharmaceutical composition comprising the same, and a method of activating P-glucocerebrosidase and treating dysfunction of P-glucocerebrosidase and diseases mediated by P-glucocerebrosidase using the same may be provided. According to the present invention, it is possible to reduce synuclein, ameliorate behavioral impairment caused by synuclein, reduce inflammation and / or prevent neuronal death. MODE FOR THE INVENTION Hereinafter, the present invention will be described in more detail through Examples. However, the Examples are only for illustratively describing the present invention, and the scope of the invention is not limited thereby. The definitions of the abbreviations used in the following Preparation Examples and Examples are as follows. DMF: N,N-dimethylformamide LiHMDS: lithium bis(trimethylsilyl)amide Pd2(dba)3: tris(dibenzylideneacetone)dipalladium(0) PyBroP: bromo-tris-pyrrolidino-phosphonium hexafluorophosphate XPhos: 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl XtalFluor-E: (diethylamino)difluorosulfonium tetrafluoroborate Preparation Example 1:   Synthesis of N-methyl-4-[(1H-1,2,3,4-tetrazol-1- yl)methyl]pyridin-2-amine Preparation Example 1A: 4-(chloromethyl)-N-methylpyridin-2-amine (2-Fluoropyridin-4-yl)methanol (1 eq) was dissolved in a sealed tube containing 40% aqueous methylamine solution (4 eq), and then stirred at 100°C for 1 hour using a microwave reactor. The reaction solution was cooled to room temperature and dried to obtain [2-(methylamino)pyridin-4-yl]methanol without further purification. The obtained compound was dissolved in acetonitrile (1.5M), and thionyl chloride (5 eq) was added. The reaction solution was stirred at room temperature for 1 hour and dried under reduced pressure to obtain the title compound without further purification. MS, found: 15 Preparation Example 1: N-methy1-4-[(1H-1,2,3,4-tetrazo1-1-y1)methy1]pyridin-2-amine The compound obtained in Preparation Example 1A (1 eq) was dissolved in DMF (0.4M), and 1H-1,2,3,4-tetrazole (1.2 eq) and cesium carbonate (3 eq) were added. The reaction solution was stirred at 90°C for 12 hours. The mixture was cooled to room temperature and diluted with water. Then, the reaction solution was extracted with ethyl acetate and then dried. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the title compound. MS, found: 191 1H-NMR (CDC13, 400MHz) 58.61(s, 1H), 88.11(d, 1H), 56.41(d, 1H), S6.14(s, 1H), 35.50(s, 2H), 34.75(br, 2H), 52.90(d, 3H) Preparation Example 2:   Synthesis of N-methyl-4-[(2H-1,2,3,4-tetrazol-1- yl)methyl]pyridin-2-amine The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in the synthesis method of Preparation Example 1, using the compound obtained in Preparation Example 1A as a starting material. MS, found: 191 Preparation Example 3:   Synthesis of N,5-dimethyl-4-[(1H-1,2,3,4-tetrazol-1- yl)methyl]pyridin-2-amine Preparation Example 3A: 4-(chloromethyl)-N,5-dimethylpyridin-2-amine The title compound was obtained in the same manner as in the synthesis method of Preparation Example 1A, using (2-fluoro-5-methylpyridin-4-yl)methanol as a starting material. MS, found: 1 1 Preparation Example 3: N,5-dimethyl-4-[(1H-1,2,3,4-tetrazol-1-yl)methyl]pyridin-2-amine The title compound was obtained in the same manner as in the synthesis method of Preparation Example 1, using the compound obtained in Preparation Example 3A as a starting material. Preparation Example 4:   Synthesis of N,5-dimethyl-4-[(2H-1,2,3,4-tetrazol-1- yl)methyl]pyridin-2-amine The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in the synthesis method of Preparation Example 1, using the compound obtained in Preparation Example 3A as a starting material. MS, found: 262 Preparation Example 5: Synthesis of N-ethyl-4-[(1H-1,2,3,4-tetrazol-1-yl)methyl]pyridin- 2-amine Preparation Example 5A: (2-fluoropyridin-4-yl)methyl methanesulfonate (2-Fluoropyridin-4-yl)methanol (1 eq) was dissolved in dichloromethane (1.5M), and methanesulfonyl chloride (1.2 eq) and triethylamine (2 eq) were added. The reaction solution was stirred at room temperature for 1 hour. The mixture was diluted with water and extracted with dichloromethane. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the title compound. MS, found: 206 Preparation Example 5B: 1-[(3-fluoropyridyl)methyl]-1H-1,2,3,4-tetrazole The compound obtained in Preparation Example 5A (1 eq) was dissolved in acetonitrile (0.3M), and 1H-1,2,3,4-tetrazole (1.2 eq) and potassium carbonate (3 eq) were added. The reaction solution was stirred under reflux for 3 days. The mixture was cooled to room temperature and diluted with water. Then, the reaction solution was extracted with ethyl acetate. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the title compound. MS, found: 1 9 Preparation Example 5: N-ethyl-4-[(1H-1,2,3,4-tetrazol-1-yl)methyl]pyridm-2-amme The compound obtained in Preparation Example 5B (1 eq) was dissolved in a sealed tube containing 66~ 2% aqueous ethylamine solution (excess, >10 eq), and then stirred at 100°C for 1 hour using a microwave reactor. The reaction solution was cooled to room temperature, diluted with water, and then extracted with ethyl acetate. The resultant was concentrated under reduced pressure to obtain the title compound without further purification. MS, found: 205 Preparation Example 6: Synthesis of N-ethyl-4-[(1H-1,2,3,4-tetrazol-2-yl)methyl]pyridin-2-amine Preparation Example 6A: 1-[(3-fluoropyridyl)methyl]-1H-1,2,3,4-tetrazole The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in the synthesis method of Preparation Example 5B, using the compound obtained in Preparation Example 5A as a starting material. MS, found: 1 9 Preparation Example 6: N-ethyl-4-[(1H-1,2,3,4-tetrazol-2-yl)methyl]pyridin-2-amine The title compound was obtained in the same manner as in the synthesis method of Preparation Example 5, using the compound obtained in Preparation Example 6A as a starting material. MS, found: 1 9 [Preparation Example Reaction Scheme 1] Ra o Ra = hydrogen, methyl Xa = fluoro, chloro Ra Each pyridine carboxylate (1 eq) was added to ethanol (0.24M), and sodium borohydride (3 eq) was added at room temperature. The reaction solution was stirred under reflux for 2 hours. The mixture was cooled to room temperature, and the reaction was quenched by adding 1N aqueous hydrochloric acid solution. Then, the reaction solution was extracted with ethyl acetate. The resultant was concentrated under reduced pressure to obtain the target compound without further purification. [Preparation Example Reaction Scheme 2] Ra Ra = hydrogen, methyl Xa = fluoro, chloro Ra 40% aqueous methylamine solution was added to each pyridinyl methanol (1 eq). The reaction solution was stirred at 100°C for 1 hour using a microwave reactor. The mixture was concentrated under reduced pressure to obtain the target compound without further purification. [Preparation Example Reaction Scheme 3] Ra 0 Ra = hydrogen, methyl Rb = hydrogen, fluoro Ra Tetrahydrofuran (3.2M) was added to each carboxylic acid (1 eq), and 1.0M borane tetrahydrofuran solution (4 eq) was added. The reaction solution was stirred at room temperature for 12 hours, and the reaction was quenched with methanol. Then, the mixture was extracted with dichloromethane. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. [Preparation Example Reaction Scheme 4] Ra Rc Ra, Rc = hydrogen, methyl Rb = hydrogen, fluoro A suitable solvent (0.3M) such as dichloromethane, tetrahydrofuran and DMF was added to each pyridinyl methanol (1 eq). Imidazole (1.5 eq) and optionally N,N-dimethylpyridin-4-amine (0.1 eq) were added to the solution. Then, tert-butyl(chloro)dimethylsilane (1.1 eq) was added to the reaction solution, and the mixture was stirred at room temperature for 30 minutes to 12 hours. The reaction was quenched by adding water to the mixture, and the mixture was extracted with dichloromethane. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. [Preparation Example Reaction Scheme 5] Ra, Rc= hydrogen, methyl Rb = hydrogen, fluoro (1r,4r)-4-tert-butylcyclohexane-1-carboxylic acid (2 eq) was dissolved in toluene (0.5M), and triethylamine (5 eq) and {[azido(phenoxy)phosphoryl]oxy}benzene (4 eq) were added. The mixture was stirred at 100°C for 30 minutes under nitrogen conditions. Each silane compound (1 eq) was added to the reaction solution, and the mixture was stirred for 12 hours. Then, the reaction solution was quenched with 1N aqueous sodium hydroxide solution and extracted with dichloromethane. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. [Preparation Example Reaction Scheme 6] Ra, Rc = hydrogen, methyl Rb = hydrogen, fluoro The urea compound (1 eq) was dissolved in methanol (0.12M), and 1.25M hydrochloric acid methanol solution (10 eq) was added. The reaction solution was stirred at room temperature for 12 hours and dried under reduced pressure. Then, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. [Preparation Example Reaction Scheme 7] Ra, Rc = hydrogen, methyl Rb = hydrogen, fluoro The urea compound (1 eq) was dissolved in dichloromethane (0.3M), and thionyl chloride (4 eq) was added. The reaction solution was stirred at room temperature for 30 minutes, quenched with methanol, and then dried under reduced pressure. Saturated aqueous sodium bicarbonate solution was added to the obtained solid, and the mixture was extracted with dichloromethane. The resultant was concentrated under reduced pressure and then optionally purified by column chromatography to obtain the target compound. Preparation Example 7: Synthesis of 3-[4-(chloromethyl)pyridin-2-yl]-1-[(1r,4r)-4-tert-butylcyclohexyl]urea Preparation Example 7 A: 4-(chloromethyl)pyridin-2-amine hydrochloride (2-Amino-4-pyridyl)methanol (1 eq) was dissolved in acetonitrile (0.5M), and thionyl chloride (2 eq) was added. The reaction solution was stirred at room temperature for 2.5 hours. Then, the reaction solution was dried under reduced pressure to obtain the title compound without further purification. MS, found: 143 Preparation Example 7: 3-[4-(chloromethyl)pyridin-2-yl]-1—r(1r,4r)-4-tert -butylcyclohexyllurea The title compound was obtained in the same manner as in Preparation Example Reaction Scheme 5, using the compound obtained in Preparation Example A as a starting material. MS, found: 324 Preparation Example 8: Synthesis of 1-[4-(chloromethyl)-2-pyridyl]-1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]urea The title compound was obtained in the same manner as in Preparation Example Reaction Schemes 2, 4, 5, 6 and , using (2-fluoropyridin-4-yl)methanol as a starting material. MS, found: 338 Preparation Example 9: Synthesis of 1-[4-(chloromethyl)-6-methyl-2-pyridyl]-1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]urea The title compound was obtained in the same manner as in Preparation Example Reaction Schemes 1, 2, 4, 5, 6 and , using methyl 2-chloro-6-methylpyridine-4-carboxylate as a starting material. MS, found: 352 Preparation Example 10: Synthesis of 3-[4-(chloromethyl)-5-fluoro-2-pyridyl]-1-[(1r,4r)-4-(tert-butyl)cyclohexyl]urea The title compound was obtained in the same manner as in Preparation Example Reaction Schemes 3, 4, 5, 6, and , using 2-amino-5-fluoropyridine-4-carboxylic acid as a starting material. MS, found: 338 [Preparation Example Reaction Scheme 8] Re 0 Rd, Re = hydrogen, methyl Rf = methyl, ethyl Re 0 Dichloromethane (0.29M) and DMF (0.29M) were added to each carboxylic acid (1 eq). Oxalyl chloride (1.2 eq) was added dropwise to the solution, and the mixture was stirred at room temperature for 1.5 hours. A 50% alcohol dichloromethane solution (1.2M) was added dropwise to the reaction solution. The reaction of the mixture was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with dichloromethane. Then, the solution was dried under reduced pressure to obtain the target compound without further purification. [Preparation Example Reaction Scheme 9] Rd, Re = hydrogen, methyl Rf = methyl, ethyl Each ester (1 eq) was dissolved in dimethyl sulfoxide (0.54M), and 2M methylamine tetrahydrofuran solution (2 eq) was added. The reaction solution was stirred at 100°C for 4 hours under sealed tube conditions. Then, the reaction solution was cooled to room temperature, diluted with water, and then extracted with ethyl acetate and saturated aqueous sodium chloride solution. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. [Preparation Example Reaction Scheme 10] Rd, Re = hydrogen, methyl Rf = methyl, ethyl (1r,4r)-4-tert-butylcyclohexane-1-carboxylic acid (2 eq) was dissolved in toluene (0.32M), and triethylamine (4 eq) and {[azido(phenoxy)phosphoryl]oxy}benzene (2 eq) were added. The reaction solution was stirred at 90°C for 1.5 hours, and each ester (1 eq) was added. Then, the reaction solution was stirred at 120°C for 3 days under sealed tube conditions. The reaction solution was cooled to room temperature, and the reaction was quenched with saturated aqueous sodium bicarbonate solution. Then, the solution was extracted with ethyl acetate and saturated aqueous sodium chloride solution. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. [Preparation Example Reaction Scheme 11] Rd, Re = hydrogen, methyl Rf = methyl, ethyl Each urea compound (1 eq) was dissolved in methanol (0.21M), and sodium borohydride (5 eq) was added. The reaction solution was stirred at room temperature for 3 hours, and the reaction was quenched by adding water. Then, the reaction solution was extracted with ethyl acetate and saturated aqueous sodium chloride solution. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. [Preparation Example Reaction Scheme 12] I H Rd, Re = hydrogen, methyl Each urea compound (1 eq) was dissolved in dichloromethane (0.24M), and triethylamine (2 eq) and methanesulfonyl chloride (1.2 eq) were added. The reaction solution was stirred at room temperature for 20 minutes, and the reaction was quenched by adding water. Then, the mixture was extracted with dichloromethane. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. Preparation Example 11: Synthesis of {2-[methyl({[(1r,4r)-4-tert- butylcyclohexyl]carbamoyl})amino]pyrimidin-4-yl}methyl methanesulfonate The title compound was obtained in the same manner as in Preparation Example Reaction Schemes 9, 10, 11 and 12, using ethyl 2-chloropyrimidine-4-carboxylate as a starting material. MS, found: 399 Preparation Example 12: Synthesis of {5-methyl-2-[methyl({[(1r,4r)-4-tert-butylcyclohexyl]carbamoyl})amino]pyrimidin-4-yl}methyl methanesulfonate The title compound was obtained in the same manner as in Preparation Example Reaction Schemes 8, 9, 10, 11 and 12, using 2-chloro-5-methylpyrimidine-4-carboxylic acid as a starting material. MS, found: 413 Preparation Example 13: Synthesis of {6-methyl-2-[methyl({[(1r,4r)-4-tert-butylcyclohexyl]carbamoyl})amino]pyrimidin-4-yl}methyl methanesulfonate N Nz N I H The title compound was obtained in the same manner as in Preparation Example Reaction Schemes 9, 10, 11 and 12, using methyl 2-chloro-6-methylpyrimidine-4-carboxylate as a starting material. MS, found: 413 [Preparation Example Reaction Scheme 13] Rg Rg = hydrogen, methyl Rg Pyridylmethanol (1 eq) was dissolved in thionyl chloride (12 eq) at 0°C and stirred at 15-20°C for 3 hours. The reaction solution was dried under reduced pressure, and saturated aqueous ammonium chloride solution was added, followed by stirring for 30 minutes. Then, the reaction solution was extracted with dichloromethane. The solution was dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure to obtain the target compound. [Preparation Example Reaction Scheme 14] Rg Rg = hydrogen, methyl Rg Chloromethylpyridine (1 eq) was dissolved in 1,2-dichloroethane (0.38M), and 1-isocyanato-4-(trifluoromethoxy)benzene (1.2 eq) was added. The reaction solution was stirred at 15-20°C for 12 hours. Then, the reaction mixture was filtered, and the solid was washed with dichloromethane to obtain the target compound. Preparation Example 14: Synthesis of 1-[4-(chloromethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The title compound was obtained in the same manner as in Preparation Example Reaction Schemes 13 and 14, using (2-amino-4-pyridyl)methanol as a starting material. MS, found: 346 Preparation Example 15: Synthesis of 1-[4-(chloromethyl)-6-methyl-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea Preparation Example 15A: (2-chloro-6-methyl-4-pyridyl)methanol 2-Chloro-6-methyl-pyridine-4-carboxylic acid (1 eq) was dissolved in tetrahydrofuran (0.3M), and 1.0M borane tetrahydrofuran solution (5 eq) was added dropwise at 0°C under nitrogen conditions. The reaction solution was warmed to 10-20°C and stirred for 18 hours. The reaction solution was cooled to 0°C, and saturated aqueous hydrochloric acid solution was added dropwise for 30 minutes with stirring. Then, the mixture was adjusted to pH =8 by adding 50% aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate and washed with saturated aqueous sodium chloride solution. Then, the solution was concentrated under reduced pressure and filtered, and then purified by column chromatography to obtain the title compound. MS, found: 158 Preparation Example 15B: (2-amino-6-methyl-4-pyridyl)methanol The compound obtained in Preparation Example 15A (1 eq), Pd2(dba)3 (2 mol%) and XPhos (4 mol%) were dissolved in tetrahydrofuran (0.5M), and 1M LiHMDS tetrahydrofuran solution (2 eq) was added under nitrogen conditions. The reaction solution was stirred at 60°C for 4 hours. Then, the reaction solution was adjusted to pH = 3-4 with 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The aqueous layer was adjusted to pH = 10 with 1N aqueous sodium hydroxide solution and extracted with ethyl acetate and dichloromethane. Then, the combined organic solvent layers were dried under reduced pressure to obtain the title compound. MS, found: 139 Preparation Example 15: 1-[4-(chloromethyl)-6-methyl-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The title compound was obtained in the same manner as in Preparation Example Reaction Schemes 13 and 14, using the compound obtained in Preparation Example 15B as a starting material. MS, found: 360 Preparation Example 16: Synthesis of (2H-tetrazol-5-yl)methanol no'^NH N=N Ethyl 2H-tetrazole-5-carboxylate (1 eq) was dissolved in tetrahydrofuran (0.35M), and lithium aluminum hydride (2 eq) was added at 0°C. Sodium sulfate was added to the reaction solution, and the mixture was stirred under the same temperature conditions for 20 minutes. Then, anhydrous sodium sulfate was added to the reaction solution, and the mixture was stirred for 20 minutes. The reaction mixture was filtered, and dichloromethane and methanol were added to the solid, which was then ground and filtered. Then, the combined organic solvent layers were dried under reduced pressure to obtain the title compound. MS, found: 101 Preparation Example 17: Synthesis of 4-(tetrazol-2-ylmethyl)pyridin-2-amine The compound obtained in Preparation Example A (1 eq), 1H-1,2,3,4-tetrazole (1.5 eq) and cesium carbonate (1.5 eq) were added to DMF (0.1 M), and the mixture was stirred at room temperature for 15 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic solvent layer was washed with saturated aqueous sodium chloride solution. Then, the solution was concentrated under reduced pressure and filtered, and then purified by column chromatography to obtain the title compound. Preparation Example 18: Synthesis of 1-[4-(chloromethyl)-2-pyridyl]-1-methyl-3-[4-(trifluoromethoxy)phenyl]urea The compound obtained in Preparation Example 1A (1 eq) was dissolved in tetrahydrofuran (0.3M), and 1-isocyanato-4-(trifluoromethoxy)benzene (2 eq) was added. The reaction solution was stirred at room temperature for 12 hours, and the reaction was quenched with water. Then, the reaction solution was extracted with ethyl acetate. Then, the solution was concentrated under reduced pressure and filtered, and then purified by column chromatography to obtain the title compound. MS, found: 360 Preparation Example 19: Synthesis of 3-[6-(chloromethyl)-2-pyridyl]-1-[(1r,4r)-4-(tert-butyl)cyclohexyl]urea Preparation Example 19A: 6-[[ tert-butyl(dimethyl)silyl]oxymethyl]pyridin-2-amine (6-Amino-2-pyridyl)methanol (1 eq) and imidazole (2.5 eq) were dissolved in DMF (0.15M), and tert-butyl(chloro)dimethylsilane (1.5 eq) was added at 0°C. The reaction solution was stirred at 25°C for 8 hours. The mixture was diluted with ethyl acetate and washed with water and saturated aqueous sodium chloride solution. Then, the solution was concentrated under reduced pressure and filtered, and then purified by column chromatography to obtain the title compound. Preparation Example 19B: trimethyl{1-methyl-1-[(6-{3-[(1r,4r)-4-( tert - butyl)cyclohexyl]ureido}-2-pyridyl)methoxy]ethyl}silane (1r,4r)-4-tert-butylcyclohexane-1-carboxylic acid (1 eq) was dissolved in toluene (0.5M), and triethylamine (3 eq) and {[azido(phenoxy)phosphoryl]oxy}benzene (2 eq) were added at room temperature. The reaction solution was stirred at 0°C for 2 hours under nitrogen conditions, and this was referred to as Mixture A. The compound obtained in Preparation Example 19A (1.2 eq) was dissolved in tetrahydrofuran (0.4M), and LiHMDS (2 eq) was added at 0°C. The reaction solution was stirred at 0°C for 1 hour under nitrogen conditions, and this was referred to as Mixture B. Mixture A was cooled to room temperature and slowly added to Mixture B at 0°C under nitrogen conditions. The mixture was stirred at 25°C for 5 hours under nitrogen conditions. The reaction solution was quenched with saturated aqueous sodium bicarbonate solution at 510°C under nitrogen conditions. Then, the reaction solution was extracted with ethyl acetate and washed with saturated aqueous sodium chloride solution. Then, the solution was concentrated under reduced pressure and filtered, and then purified by column chromatography to obtain the title compound. MS, found: 420 Preparation Example 19C: (6-{3-[(1r,4r)-4-( tert -butyl)cyclohexyl]ureido}-2- pyridyl)methanol The compound obtained in Preparation Example 19B (1 eq) was dissolved in methanol (0.04M), and camphorsulfonic acid (1.08 eq) was added at room temperature under nitrogen conditions. The reaction solution was stirred at 50°C for 2 hours. An anion exchange resin was added to the mixture, and the mixture was stirred at 25°C for 1 hour. The mixture was filtered and dried. The obtained mixture was purified by reverse-phase high-performance liquid chromatography to obtain the title compound. MS, found: 306 Preparation Example 19: 3-[6-(chloromethyl)-2-pyridyl]-1-[(1r,4r)-4-( tert -butyl)cyclohexyl]urea The compound obtained in Preparation Example 19C (1 eq) was dissolved in dichloromethane (0.3M), and thionyl chloride (4 eq) was added. The reaction solution was stirred at room temperature for 2 hours. The mixture was dried and diluted with saturated aqueous sodium bicarbonate solution. Then, the mixture was extracted with dichloromethane and dried under reduced pressure to obtain the title compound without further purification. MS, found: 324 Preparation Example 20: Synthesis of 1-(1-adamantyl)-3-[4-(chloromethyl)-2-pyridyl]urea The compound obtained in Preparation Example A (1 eq), 4-nitrophenyl chloroformate (1 eq) and diisopropylethylamine (4 eq) were dissolved in dichloromethane (0.3M), and adamantan-1-amine (1 eq) was added, and the mixture was stirred at room temperature for 12 hours. Water was added to the reaction solution, and the mixture was extracted with dichloromethane. The obtained organic solvent layer was concentrated under reduced pressure and dried, and then purified by column chromatography to obtain the title compound. MS, found: 320 Preparation Example 21: Synthesis of 3-[4-(2-hydroxyethyl)pyridin-2-yl]-3-methyl-1- [(1r,4r)-4-tert-butylcyclohexyl]urea Preparation Example 21A: 4-{2-[( tert-butyldimethylsilyl)oxy]ethyl}pyridine 2-(Pyridin-4-yl)ethan-1-ol hydrochloride (1 eq) and imidazole (2.5 eq) were dissolved in tetrahydrofuran (0.2M), and DMF (0.5M) was added. To the solution, tert-butyl(chloro)dimethylsilane (1.5 eq) was added at 0°C, and the mixture was stirred at 25°C for 12 hours. The mixture was diluted with ethyl acetate and washed with water and saturated aqueous sodium chloride solution. Then, the solution was concentrated under reduced pressure and filtered, and then purified by column chromatography to obtain the title compound. Preparation Example 21B: 4-{2-[( tert-butyldimethylsilyl)oxy]ethyl}pyridin-1-ium-1-olate The compound obtained in Preparation Example 21A (1 eq) and magnesium monoperoxyphthalate (1.5 eq) were dissolved in methanol (0.3M) and stirred at 60°C for 3 hours. The reaction solution was cooled to room temperature and filtered to remove solids. The filtrate was dried, diluted with dichloromethane, and then extracted. Then, the solution was dried under reduced pressure to obtain the title compound without further purification. Preparation Example 21C: 4-{2-[( tert-butyldimethylsilyl)oxy]ethyl}-N- methylpyridin-2-amine The compound obtained in Preparation Example 21B (1 eq) and PyBroP (1.3 eq) were dissolved in a sealed tube containing 2M methylamine tetrahydrofuran solution (10 eq) and stirred at room temperature for 12 hours. The reaction solution was diluted with dichloromethane and then extracted. Then, the solution was dried under reduced pressure to obtain the title compound without further purification. Preparation Example 21D: 3-(4-{2-[( tert-butyldimethylsilyl)oxy1ethyl}pyridin-2-yl)- 3 -methyl-1-[(1 r,4r)-4-tert-butylcyclohexyllurea (1r,4r)-4-tert-butylcyclohexane-1-carboxylic acid (1.3 eq) was dissolved in toluene (0.5M), and triethylamine (3 eq) and {[azido(phenoxy)phosphoryl1oxy}benzene (1.3 eq) were added at room temperature. The reaction solution was stirred at 100°C for 1 hour under nitrogen conditions, and this was referred to as Mixture A. The compound obtained in Preparation Example 21C (1 eq) was added to Mixture A and stirred at 100°C for 12 hours. Then, the reaction was quenched with 1N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The obtained mixture was concentrated under reduced pressure and dried, and then purified by column chromatography to obtain the title compound. Preparation Example 21: 3-[4-(2-hvdroxyethyl)pyridm-2-yl1-3-methvl-1-^(1r,4r)-4-tert-butylcyclohexyl] urea The compound obtained in Preparation Example 21D (1 eq) was dissolved in 1.25M hydrochloric acid methanol solution (4 eq) and stirred at room temperature for 12 hours. The reaction was quenched with saturated aqueous sodium bicarbonate solution, and the reaction solution was extracted with dichloromethane. The obtained solution was concentrated under reduced pressure and dried, and then purified by column chromatography to obtain the title compound. MS, found: 333 [Reaction Scheme 1] DPPA, TEA Tol or ,Rj Rh = hydrogen, methyl Ri = methyl, ethyl Rj = substituted alkylcyclohexyl, cyclohexyl, phenyl Toluene (0.5M) was added to each carboxylic acid (2 eq). Triethylamine (5 eq) and {[azido(phenoxy)phosphoryl]oxy}benzene (4 eq) were added to the solution, and the mixture was stirred at 90°C for 2 hours. Each amine (1 eq) was added to the reaction solution, and the mixture was stirred at 90°C for 12 hours. The mixture was cooled to room temperature, and the reaction was quenched with saturated aqueous sodium bicarbonate solution. The solution was extracted with ethyl acetate, dried under reduced pressure, and then purified by column chromatography to obtain the target compound. Example 1: Synthesis of 1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole The title compound was obtained in the same manner as in Reaction Scheme 1, using (1r,4r)-4-tert-butylcyclohexane-1-carboxylic acid and the compound obtained in Preparation Example 1 as starting materials (55% yield). 1H-NMR (CDC13, 400MHz) 89.78(d, 1H), 88.67(s, 1H), 88.25(d, 1H), 86.86(s, 1H), 86.72(d, 1H), 85.63(s, 2H), 83.61(m, 1H), 83.36(s, 3H), 82.10(d, 2H), 81. 79(d, 2H), 81.15(m, 4H), 81.02(m, 1H), 80.9 (s, 9H) Example 2: Synthesis of 1-[(2-{1-ethyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 1, using (1r,4r)-4-tert-buty1cyc1ohexane-1-carboxy1ic acid and the compound obtained in Preparation Examp1e 5 as starting materia1s (13% yie1d). 1H-NMR (CDC13, 400MHz) 88. 0(s, 1H), 88.26(d, 1H), 86.92(s, 1H), 86. 6(d, 1H), 85.63(s, 2H), 83.96(q, 2H), 83.61(m, 1H), 83.10(s,  H), 82.09(d, 2H), 81. 9(d, 2H), 81.11(m, 10H), 80.88(s, 10H) Example 3: Synthesis of 1-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert- butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 1, using (1r,4r)-4-tert-buty1cyc1ohexane-1-carboxy1ic acid and the compound obtained in Preparation Examp1e 3 as starting materia1s (12% yie1d). 1H-NMR (CDC13, 400MHz) 89.53(d, 1H), 88.58(s, 1H), 88.13(s, 1H), 86.68(s, 1H), 85.59(s, 2H), 83.60(m, 1H), 83.30(s, 3H), 82.25(s, 3H), 82.10(d, 2H), 81.89(d, 2H), 81.24(m, 4H), 81.19(m, 1H), 81.12(s, 9H) Example 4: Synthesis of 2-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert- butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole The title compound was obtained in the same manner as in Reaction Scheme 1, using (1r,4r)-4-tert-butylcyclohexane-1-carboxylic acid and the compound obtained in Preparation Example 4 as starting materials (21% yield). 1H-NMR (CDC13, 400MHz) 39.66(d, 1H), 38.56(s, 1H), 38.10(s, 1H), 36.74(s, 1H), 35.79(s, 2H), 33.59(m, 1H), 33.30(s, 3H), 32.32(s, 3H), 32.11(d, 2H), 31. 78(d, 2H), 31.14(m, 4H), 31.0 (m, 1H), 31.00(s, 9H) Example 5: Synthesis of 2-[(2-{1-methyl-3-[(1s,4s)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 1, using (1s,4s)-4-tert-buty1cyc1ohexane-1-carboxy1ic acid and the compound obtained in Preparation Examp1e 2 as starting materia1s (31% yie1d). 1H-NMR (CDC13, 400MHz) 310. (s, 1H), 38.58(s, 1H), 38.23(d, 1H), 36.91(s, 1H), 38.583(d, 1H), 35.82(s, 2H), 34.13(m, 1H), 33.38(s, 3H), 31.84(d, 2H), 31.65(d, 2H), 31.1.48(t, 2H), 31.26(m, 2H), 31.1 (m, 1H), 31.15(s, 9H) Example 6: Synthesis of 1-({2-[3-(4,4-difluorocyclohexyl)-1-methylureido]-4- pyridyl}methyl)-1H-tetrazole The title compound was obtained in the same manner as in Reaction Scheme 1, using 4,4-difluorocyclohexane-1-carboxylic acid and the compound obtained in Preparation Example 1 as starting materials (12% yield). 1H-NMR (CDC13, 400MHz) 510.2(d, 1H), 58.68(s, 1H), 58.27(d, 1H), 56.85(s, 1H), 56.77(d, 1H), 55.64(s, 2H), 53.92(m, 1H), 53.37(s, 3H), 52.03(m, 4H), 51.84(m, 2H), 51.6 7(m, 2H) Example 7: Synthesis of 2-[(2-{1-methyl-3-[(1r,4r)-4- (trifluoromethyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole F The tit1e compound was obtained in the same manner as in Reaction Scheme 1, using (1r,4r)-4-(trif1uoromethy1)cyc1ohexanecarboxy1ic acid and the compound obtained in Preparation Examp1e 2 as starting materia1s (24% yie1d). 1H-NMR (CDC13, 400MHz) 510.1(d, 1H), 58.58(s, 1H), 58.23(d, 1H), 56.90(s, 1H), 56.83(d, 1H), 55.82(s, 2H), 53.66(m, 1H), 53.3 (s, 3H), 52.18(d, 2H), 52.01(d, 3H), 51.4 (q, 2H), 51.41(q, 2H) Example 8: Synthesis of 2-[(2-{1-methyl-3-[(1r,4r)-4-isopropylcyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 1, using (1r,4r)- -hydroxy-p-menthan- -one and the compound obtained in Preparation Examp1e 2 as starting materia1s (19% yie1d). 1H-NMR (CDC13, 400MHz) 59.96(s, 1H), 58.58(s, 1H), 58.24(d, 1H), 56.91(s, 1H), 56.83(d, 1H), 55.82(s, 2H), 53.63(m, 1H), 53.3 (s, 3H), 52.0 (d, 2H), 51. 3(d, 2H), 51.43(m, 1H), 31.21(m, 5H), 31.06(s, 6H) Example 9: Synthesis of 1-[(2-{1-methyl-3-(6-spiro[2.5]octyl)ureido}-4-pyridyl)methyl]-1H-tetrazole The title compound was obtained in the same manner as in Reaction Scheme 1, using spiro[2.5]octane-6-carboxylic acid and the compound obtained in Preparation Example 1 as starting materials (4% yield). 1H-NMR (CDC13, 400MHz) 39.98(d, 1H), 38.67(s, 1H), 38.29(d, 1H), 36.87(s, 1H), 36.73(d, 1H), 35.62(s, 2H), 33.85(m, 1H), 33.3 7(s, 3H), 31.92(m, 2H), 31.63(m, 2H), 31.42(m, 2H), 31.11(d, 2H), 30.29(m, 2H), 30.22(m, 2H) Example 10: Synthesis of 1-[(2-{1-methyl-3-(7-spiro[3.5]nonyl)ureido}-4-pyridyl)methyl]-1H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 1, using spiro[3.5]nonane- -carboxy1ic acid and the compound obtained in Preparation Examp1e 1 as starting materia1s (4% yie1d). 1H-NMR (CDC13, 400MHz) 39.8 (s, 1H), 38.65(s, 1H), 38.26(d, 1H), 36.85(s, 1H), 36. 2(d, 1H), 35.61(s, 2H), 33. 1(m, 1H), 33.34(s, 3H), 31.83(m, 4H), 31.68(m, 6H), 31.43(m, 2H), 31.11(m, 2H) Example 11: Synthesis of 1-methyl-3-[(4-methylcyclohexyl)methyl]-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea ,N~N The title compound was obtained in the same manner as in Reaction Scheme 1, using 2-(4-methylcyclohexyl)acetic acid and the compound obtained in Preparation Example 1 as starting materials (32% yield). 1H-NMR (CDC13, 400MHz) 510.03-10.01(m, 1H), 58.68(s, 1H), 58.28-8.26(m, 1H), 56.86(s, 1H), 56.74(d, 1H), 55.63(s, 2H), 53.3 7(s, 3H), 53.32-3.29(m, 1H), 53.20(t, 1H), 51.79-1.65(m, 4H), 51.54-1.41(m, 3H), 51.35-1.26(m, 1H), 51.04-0.86(m, 5H) Example 12: Synthesis of 3-(4-cyclopropylphenyl)-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 1, using 4-cyc1opropy1benzoic acid and the compound obtained in Preparation Examp1e 1 as starting materia1s. 1H-NMR (CDC13, 400MHz) 512.42(s, 1H), 58. 2(s, 1H), 58.34(d, 1H), 5 .41(d, 2H), 5 .03(d, 2H), 56.89(s, 1H), 56. 9(d, 1H), 55.63(s, 2H), 53.41(s, 3H), 51.89(m, 1H), 51.68(s, 1H), 51.26(t, 1H), 50.94(q, 2H), 50.91(q, 2H) Example 13: Synthesis of 1-methyl-3-(4-propylphenyl)-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 1, using 4-propy1benzoic acid and the compound obtained in Preparation Examp1e 1 as starting materials. 1H-NMR (CDC13, 400MHz) 612.43(s, 1H), 68.77(s, 1H), 88.32(d, 1H), 67.43(d, 2H), 87.13(d, 2H), 66.91(s, 1H), 66.78(d, 1H), 65.62(s, 2H), 63.39(s, 3H), 62.56(t, 2H), 61.66(q, 2H), 60.94(t, 3H) [Reaction Scheme 2] Rk = hydrogen, fluoro Rl, Rm = hydrogen, methyl Rn = hydrogen, alkyl, hydroxymethyl, trifluoromethyl n-n NyNH Rn or Rm H The ch1orine-substituted compound (1 eq) was disso1ved in DMF, and 1H-1,2,3,4-tetrazo1e (1.2 eq) and cesium carbonate (2 eq) were added. The reaction so1ution was stirred at 90°C for 12 hours. The mixture was coo1ed to room temperature, and the reaction was quenched with saturated aqueous sodium bicarbonate so1ution. Then, the reaction so1ution was extracted with dich1oromethane. The resu1tant was concentrated under reduced pressure and then purified by co1umn chromatography to obtain the target compound. Example 14: Synthesis of 2-[(2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4- pyridyl)methyl]-2H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 2, using 1H-1,2,3,4-tetrazo1e and the compound obtained in Preparation Examp1e as starting materia1s (24% yie1d). 1H-NMR (CDC13, 400MHz) 69.10(s, 1H), 68.93(s, 1H), 68.56(s, 1H), 68.13(d, 1H), 66.86(s, 1H), 66. 0(d, 1H), 65.  (s, 2H), 63.63(m, 1H), 62.13(d, 2H), 61.82(d, 2H), 61.13(m, 4H), 50.99(m, 1H), 50.87(s, 9H) Example 15: Synthesis of 1-[(2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 2, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example as starting materials (34% yield). 1H-NMR (CDC13, 400MHz) 58.62(m, 1H), 58.18(d, 1H), 57.52(s, 1H), 56.64(m, 2H), 55.56(s, 2H), 53.64(m, 1H), 52.12(d, 3H), 51.81(d, 3H), 51.14(m, 8H), 50.86(m, 11H) Example 16: Synthesis of 5-methyl-2-[(2-{1-methyl-3-[(1r,4r)-4-(tert- butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole H The tit1e compound was obtained in the same manner as in Reaction Scheme 2, using 5-methy1-2H-1,2,3,4-tetrazo1e and the compound obtained in Preparation Examp1e 8 as starting materia1s (11% yie1d). 1H-NMR (CDC13, 400MHz) 59.86(d, 1H), 58.21(d, 1H), 56.89(s, 1H), 56.80(d, 1H), 55. 0(s, 2H), 53.64(m, 1H), 53.36(s, 3H), 52.54(s, 3H), 52.10(d, 2H), 51. 8(d, 2H), 51.56(s, 3H), 51.12(m, 9H), 50.99(s, 10H) Example 17: Synthesis of 5-methyl-1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 2, using 5-methyl-2H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 8 as starting materials (20% yield). 1H-NMR (CDC13, 400MHz) 59.75(d, 1H), 58.22(d, 1H), 56.77(s, 1H), 56.61(d, 1H), 55.49(s, 2H), 55.49(s, 2H), 53.62(m, 1H), 53.35(s, 3H), 52.50(s, 3H), 52.11(d, 2H), 52.01(m, 1H), 51. 9(d, 2H), 51.5 (s, 3H), 51.11(m, 9H), 51.03(s, 10H) Example 18: Synthesis of 2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4- pyridyl)methyl]-5-propyl-2H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 2, using 5-propy1-2H-1,2,3,4-tetrazo1e and the compound obtained in Preparation Examp1e 8 as starting materia1s (16% yie1d). 1H-NMR (CDC13, 400MHz) 59.89(s, 1H), 58.21(d, 1H), 56. 9(m, 2H), 55. 1(s, 2H), 53.62(m, 1H), 53.35(s, 3H), 52.86(t, 2H), 52.10(d, 2H), 51.  (m, 4H), 51.51(s, 2H), 51.20(m, 6H), 51.11(t, 4H), 51.02(s, 10H) Example 19: Synthesis of 1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4- pyridyl)methyl]-5-propyl-1H-tetrazole The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 2, using 5-propyl-2H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 8 as starting materials (16% yield). 1H-NMR (CDC13, 400MHz) 59.80(s, 1H), 88.22(d, 1H), 56.75(s, 1H), 86.61(d, 1H), 85.49(s, 2H), 83.63(m, 1H), 53.34(s, 3H), 52.72(t, 2H), 82.10(d, 2H), 82.01(s, 5H), 51. 76(m, 4H), 51.42(m, 5H), 51.21(m, 4H), 51.15(s, 10H) Example 20: Synthesis of 2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-(trifluoromethyl)-2H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 2, using 5-(trif1uoromethy1)-2H-tetrazo1e and the compound obtained in Preparation Examp1e 8 as starting materia1s (48% yie1d). 1H-NMR (CDC13, 400MHz) 59. 8(s, 1H), 58.26(d, 1H), 56.9 (s, 1H), 56.86(d, 1H), 55.83(s, 2H), 53.63(m, 1H), 53.39(s, 3H), 52.11(d, 2H), 51. 9(d, 2H), 51.55(s, 6H), 51.1 (m, H), 50.98(s, 10H) Example 21: Synthesis of 1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-(trifluoromethyl)-1H-tetrazole The tit1e compound, which is a regioisomer, was purified through co1umn chromatography in the same manner as in Reaction Scheme 2, using 5-(trif1uoromethy1)-2H-tetrazo1e and the compound obtained in Preparation Examp1e 8 as starting materia1s (4% yie1d). 1H-NMR (CDC13, 400MHz) 59. 5(d, 1H), 58.25(s, 1H), 56.85(s, 1H), 56. 2(d, 1H), 85.68(s, 2H), 83.64(m, 1H), 83.36(s, 3H), 82.11(d, 2H), 81.79(d, 2H), 81.54(s, 11H), 81.12(m, 11H), 80.85(s, 11H) Example 22: Synthesis of 2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole H The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 2, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 8 as starting materials (34% yield). 1H-NMR (CDCl3, 400MHz) 89.84(d, 1H), 88.5 (s, 1H), 88.22(d, 1H), 86.89(s, 1H), 86.80(d, 1H), 85.80(s, 2H), 83.63(m, 1H), 83.36(s, 3H), 82.10(d, 2H), 81. 8(d, 2H), 81.15(m, 5H), 80.99(t, 1H), 80.85(s, 10H) Example 23: Synthesis of {1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4- pyridyl)methyl]-1H-tetrazol-5-yl}methanol OH The title compound was obtained in the same manner as in Reaction Scheme 2, using (2H-tetrazol-5-yl)methanol and the compound obtained in Preparation Example 8 as starting materials (12% yield). 1H-NMR (DMSO-d6, 400MHz) 89.18(d, 1H), 88.26(d, 1H), 8 .19(s, 1H), 86.83(d, 1H), 85.98(s, 1H), 85. 5(s, 2H), 84.83(s, 2H), 83.45(m, 1H), 83.39(s, 3H), 81.94(d, 2H), 81. 3(d, 2H), 81.23(m, 2H), 81.20(m, 3H), 81.16(s, 9H) Example 24: Synthesis of {2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazol-5-yl}methanol The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 2, using (2H-tetrazol-5-yl)methanol and the compound obtained in Preparation Example 8 as starting materials (13% yield). 1H-NMR (DMSO-d6, 400MHz) 59.12(d, 1H), 58.28(d, 1H), 57.28(s, 1H), 86.84(d, 1H), 55.99(s, 2H), 55.62(t, 1H), 54.67(d, 2H), 53.47(m, 1H), 53.27(s, 3H), 51.9 7(d, 2H), 51. 3(d, 2H), 51.24(q, 2H), 51.14(q, 3H), 51.06(s, 9H) Example 25: Synthesis of [2-({2-[methyl({[(1r,4r)-4-tert- butylcyclohexyl]carbamoyl})amino]pyridin-4-yl}methyl)-2H-1,2,3,4-tetrazol-5-yl]methyl N,N-dimethylcarbamate The compound obtained in Example 24 (1 eq) and 1-(1H-imidazole-1-carbonyl)-1H-imidazole (1.5 eq) were dissolved in dichloromethane and stirred at room temperature for 1 hour. The reaction solution was quenched with water and extracted with ethyl acetate. The solution was dried under reduced pressure and dissolved in tetrahydrofuran. Then, 2M dimethylamine tetrahydrofuran solution (1.5 eq) and triethylamine (2 eq) were added to the solution, and the mixture was stirred at room temperature for 2 hours and then quenched with saturated aqueous sodium bicarbonate solution. The reaction solution was extracted with ethyl acetate and dried. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the title compound (3 % yield). 1H-NMR (CDCl3, 400MHz) 59.8 (d, 1H), 58.22(d, 1H), 56.88(s, 1H), 56.83(d, 1H), 55. 6(s, 2H), 55.38(s, 2H), 53.59(m, 1H), 53.36(s, 3H), 52.93(d, 6H), 52.10(d, 2H), 51. 8(d, 2H), 51.21(m, 4H), 51.11(t, 1H), 51.08(s, 9H) Example 26: Synthesis of 1-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert- butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole The title compound was obtained in the same manner as in Reaction Scheme 2, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 9 as starting materials (1 % yield). 1H-NMR (CDC13, 400MHz) 89.02(s, 1H), 8 7.10(s, 1H), S6.85(s, 1H), 85.77(s, 2H), 83.56(t, 1H), 83.42(s, 3H), 82.56(s, 3H), 82.06(d, 2H), 81.81(d, 2H), 81.16(m, 6H), 80.85(s, 9H) Example 27: Synthesis of 2-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert- butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole The tit1e compound, which is a regioisomer, was purified through co1umn chromatography in the same manner as in Reaction Scheme 2, using 1H-1,2,3,4-tetrazo1e and the compound obtained in Preparation Examp1e 9 as starting materia1s (16% yie1d). 1H-NMR (CDC13, 400MHz) 810.3(d, 1H), 88.56(s, 1H), 86.66(d, 2H), 85. 6(s, 2H), 83.59(m, 1H), 83.34(s, 3H), 82.44(s, 3H), 82.14(d, 2H), 81. 8(d, 2H), 81.21(m, 5H), 80.85(s, 10H) Example 28: Synthesis of 2-[(5-fluoro-2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole The title compound was obtained in the same manner as in Reaction Scheme 2, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 10 as starting materials (28% yield). 1H-NMR (CDC13, 400MHz) 58.59(s, 1H), 58.33(s, 1H), 58.09(s, 1H), 5 7.18(s, 1H), 56.54(d, 1H), 55.86(s, 2H), 53.60(m, 1H), 52.10(d, 2H), 51.80(d, 2H), 51.10(m, 5H), 51.03(m, 1H), 50.86(s, 9H) Example 29: Synthesis of 1-[(5-fluoro-2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole The tit1e compound, which is a regioisomer, was purified through co1umn chromatography in the same manner as in Reaction Scheme 2, using 1H-1,2,3,4-tetrazo1e and the compound obtained in Preparation Examp1e 10 as starting materia1s (31% yie1d). 1H-NMR (CDC13, 400MHz) 58. 0(s, 1H), 58.10(m, 2H), 5 . 8(s, 1H), 56. 6(s, 1H), 55.62(s, 2H), 53.63(m, 1H), 52.10(d, 2H), 51.81(d, 2H), 51.16(m, 5H), 51.01(m, 1H), 50.86(s, 10H) [Reaction Scheme 3] Ro, Rp = hydrogen, methyl Rq = hydrogen, methyl, hydroxymethyl, phe nyl or Ro Each ch1orine-substituted compound (1 eq), each tetrazo1e (4 eq) and cesium carbonate (3.3 eq) were disso1ved in DMF (0.4M) and stirred at 0°C for 15 hours. The reaction so1ution was cooled to room temperature, diluted with water, and then extracted with ethyl acetate. The organic solvent layer was washed with saturated aqueous sodium chloride solution. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. Example 30: Synthesis of 1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea H H The title compound was obtained in the same manner as in Reaction Scheme 3, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 14 as starting materials. 1H-NMR (DMSO-d6, 400MHz) 810.41(s, 1H), 59.60(m, 2H), 88.28(d, 1H), 57.63(d, 2H), 37.43(s, 1H), 37.32(d, 2H), 36.89(d, 1H), 35.80(s, 2H) Example 31: Synthesis of 1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 3, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 14 as starting materials. 1H-NMR (DMSO-d6, 400MHz) 310.30(s, 1H), 59.50(s, 1H), 39.09(s, 1H), 58.28(d, 1H), 87.61(d, 2H), 87.43(s, 1H), 37.32(d, 2H), S6.90(d, 1H), 36.06(s, 2H) Example 32: Synthesis of 1-[4-[(5-methyltetrazol-1-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The title compound was obtained in the same manner as in Reaction Scheme 3, using 5-methyl-1H-tetrazole and the compound obtained in Preparation Example 14 as starting materials (2 % yield). 1H-NMR (DMSO-d6, 400MHz) 510.36(s, 1H), 59.49(s, 1H), 58.27(d, 1H), 57.64-7.57(m, 2H), 57.38-7.28(m, 3H), 56.87-6.80(m, 1H), 55.73(s, 2H), 52.50(s, 3H) Example 33: Synthesis of 1-[4-[(5-methyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4- (trifluoromethoxy)phenyl]urea H H The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 3, using 5-methyl-1H-tetrazole and the compound obtained in Preparation Example 14 as starting materials (25% yield). 1H-NMR (CDCl3, 400MHz) 511.64(s, 1H), 58.2 (d, 1H), 5 .61(d, 2H), 5 .22(d, 2H), 56.89(d, 1H), 56. 0(s, 1H), 55. 2(s, 2H), 52.5 (s, 3H) Example 34: Synthesis of 1-[4-[[5-(hydroxymethyl)tetrazol-1-yl]methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea OH The title compound was obtained in the same manner as in Reaction Scheme 3, using the compounds obtained in Preparation Example 14 and Preparation Example 16 as starting materials ( % yield). 1H-NMR (DMSO-d6, 400MHz) 510.3 (s, 1H), 59.50(s, 1H), 58.26(d, 1H), 5 .6 - 7.55(m, 2H), 8 7.41(s, 1H), 87.31(d, 2H), S6.84(dd, 1H), 85.95(t, 1H), 85.76(s, 2H), 84.82(d, 2H) Example 35: Synthesis of 1-[4-[[5-(hydroxymethyl)tetrazol-2-yl]methyl]-2-pyridyl]-3-[4- (trifluoromethoxy)phenyl]urea The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 3, using the compounds obtained in Preparation Example 14 and Preparation Example 16 as starting materials (9% yield). 1H-NMR (DMSO-d6, 400MHz) 810.34(s, 1H), 89.52(s, 1H), 88.28(d, 1H), 8 .64-.58(m, 2H), 8 .50(s, 1H), 8 .31(d, 2H), 86.90(dd, 1H), 85.99(s, 2H), 85.64(t, 1H), 84.68(d, 2H) Example 36: Synthesis of 1-[6-methyl-4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4- (trifluoromethoxy)phenyl]urea The title compound was obtained in the same manner as in Reaction Scheme 3, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 15 as starting materials (1 % yield). 1H-NMR (Acetone, 400MHz) 811. 0(s, 1H), 89.31(s, 1H), 88.86(s, 1H), 8 . 9- . 1(m, 2H), 8 .30(d, 2H), 86.91(s, 1H), 86.86(s, 1H), 85.84(s, 2H), 82.55(s, 3H) Example 37: Synthesis of 1-[6-methyl-4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea H H The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 3, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 15 as starting materials (19% yield). 1H-NMR (Acetone, 400MHz) 811. 70(s, 1H), 88.86(s, 1H), S8.84(s, 1H), 87.80-7.71(m, 2H), 87.30(d, 2H), 86.95(s, 1H), 86.87(s, 1H), 86.00(s, 2H), 82.56(s, 3H) Example 38: Synthesis of 1-[6-methyl-4-[(5-methyltetrazol-1-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The title compound was obtained in the same manner as in Reaction Scheme 3, using 5-methyl-1H-tetrazole and the compound obtained in Preparation Example 15 as starting materials (34% yield). 1H-NMR (Acetone, 400MHz) 811. 5(s, 1H), 88.84(s, 1H), 8 .80- .69(m, 2H), 8 .30(d, 2H), 86.84-6. 6(m, 2H), 85. 2(s, 2H), 82.5 (s, 3H), 82.56(s, 3H) Example 39: Synthesis of 1-[6-methyl-4-[(5-methyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea H H The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 3, using 5-methyl-1H-tetrazole and the compound obtained in Preparation Example 15 as starting materials (31% yield). 1H-NMR (Acetone, 400MHz) 510.6 7(s, 1H), 59.54(s, 1H), 57.60(d, 2H), 57.31(d, 2H), 56.76(s, 1H), 55.88(s, 2H), 52.47(s, 3H), 52.43(s, 3H) Example 40: Synthesis of 1-[4-[[5-(hydroxymethyl)tetrazol-1-yl]methyl]-6-methyl-2- pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The title compound was obtained in the same manner as in Reaction Scheme 3, using the compounds obtained in Preparation Example 15 and Preparation Example 16 as starting materials, and was purified through preparative high-performance liquid chromatography (5% yield). 1H-NMR (DMSO-d6, 400MHz) 510. 4(s, 1H), 9.65(s, 1H), 5 .65- .5 (m, 2H), 5 .32(d, 2H), 5 .20(s, 1H), 56. 4(s, 1H), 55. 4(s, 2H), 54.82(s, 2H), 52.44(s, 3H) Example 41: Synthesis of 1-[4-[[5-(hydroxymethyl)tetrazol-2-yl]methyl]-6-methyl-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea Synthesis was performed in the same manner as in Reaction Scheme 3, using the compounds obtained in Preparation Example 15 and Preparation Example 16 as starting materials, and the title compound, which is a regioisomer, was purified through preparative high-performance liquid chromatography (5% yield). 1H-NMR (DMSO-d6, 400MHz) 510.66(s, 1H), 59.58(s, 1H), 5 .64- .5 (m, 2H), 5 .32(d, 2H), 5 .24(s, 1H), 56. 8(s, 1H), 55.93(s, 2H), 54.68(s, 2H), 52.44(s, 3H) Example 42: Synthesis of 1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The title compound was obtained in the same manner as in Reaction Scheme 3, using 1H-1,2,3,4-tetrazole and the compound obtained in Preparation Example 18 as starting materials (11% yield). 1H-NMR (CDC13, 400MHz) 312.68(s, 1H), 38.68(s, 1H), 38.38(d, 1H), 37.58(d, 2H), 3 7.19(d, 2H), 36.92(s, 1H), 36.85(d, 1H), 35.67(s, 2H), 33.45(s, 3H) Example 43: Synthesis of 1-methyl-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The tit1e compound, which is a regioisomer, was purified through co1umn chromatography in the same manner as in Reaction Scheme 3, using 1H-1,2,3,4-tetrazo1e and the compound obtained in Preparation Examp1e 18 as starting materia1s (6% yie1d). 1H-NMR (CDC13, 400MHz) 312. 3(s, 1H), 38.60(s, 1H), 38.36(d, 1H), 3 .58(d, 2H), 3 .18(d, 2H), 36.99(s, 1H), 36.95(d, 1H), 35.86(s, 2H), 33.46(s, 3H) Example 44: Synthesis of 1-[4-[(5-phenyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4- (trifluoromethoxy)phenyl]urea H The tit1e compound was obtained in the same manner as in Reaction Scheme 3, using 5-pheny1-2H-tetrazo1e and the compound obtained in Preparation Examp1e 18 as starting materia1s. 1H-NMR (DMSO-d6, 400MHz) 310.43(s, 1H), 39.55(s, 1H), 38.31(d, 1H), 38.09(d, 2H), 3 .62(m, 5H), 3 .48(s, 1H), 3 .32(d, 2H), 36.98(d, 1H), 36.11(s, 2H) [Reaction Scheme 4] Rr, Rs = hydrogen, methyl n=n n^nh or Each methanesulfonyl intermediate (1 eq), 1H-1,2,3,4-tetrazole (1.2 eq) and potassium carbonate (2 eq) were added to acetonitrile (0.12M). The reaction solution was stirred at 80°C for 2 hours. The reaction solution was cooled to room temperature, and the reaction was quenched with saturated aqueous sodium bicarbonate solution. Then, the reaction solution was extracted with ethyl acetate and saturated aqueous sodium chloride solution. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound and a regioisomer thereof. Example 45: Synthesis of 1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4- pyrimidinyl)methyl]-1H-tetrazole The title compound was obtained in the same manner as in Reaction Scheme 4, using the compound obtained in Preparation Example 11 as a starting material (43% yield). 1H-NMR (CDC13, 400MHz) 59.62(d, 1H), 58.83(s, 1H), 58.51(d, 1H), 56.74(d, 1H), 55.66(s, 2H), 53.60(m, 1H), 53.42(s, 3H), 52.09(d, 2H), 51.80(d, 2H), 51.24(m, 4H), 51.01(m, 1H), 50.86(s, 9H) Example 46: Synthesis of 2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole I H The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Reaction Scheme 4, using the compound obtained in Preparation Example 11 as a starting material (40% yield). 1H-NMR (CDC13, 400MHz) 59.64(d, 1H), 58.62(s, 1H), S8.51(d, 1H), 56.62(d, 1H), 55.87(s, 2H), 53.60(m, 1H), 53.46(s, 3H), 52.09(d, 2H), 51.80(d, 2H), 51.20(m, 4H), 51.12(m, 1H), 51.10(s, 9H) Example 47: Synthesis of 1-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert- butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-1H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 4, using the compound obtained in Preparation Examp1e 12 as a starting materia1 (40% yie1d). 1H-NMR (CDC13, 400MHz) 59.52(d, 1H), 58.82(s, 1H), 58.34(s, 1H), 55.68(s, 2H), 53.5 (m, 1H), 53.30(s, 3H), 52.36(s, 3H), 52.09(d, 2H), 51. 9(d, 2H), 51.22(m, 4H), 51.18(m, 1H), 51.16(s, 9H) Example 48: Synthesis of 2-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert- butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole H The tit1e compound, which is a regioisomer, was purified through co1umn chromatography in the same manner as in Reaction Scheme 4, using the compound obtained in Preparation Example 12 as a starting material (36% yield). 1H-NMR (CDC13, 400MHz) 89.51(d, 1H), 88.58(s, 1H), 88.36(s, 1H), 85.87(s, 2H), 83.56(m, 1H), 83.32(s, 3H), 82.33(s, 3H), 82.06(d, 2H), 81.80(d, 2H), 81.22(m, 4H), 81.14(m, 1H), 81.12(s, 9H) Example 49: Synthesis of 1-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-1H-tetrazole The tit1e compound was obtained in the same manner as in Reaction Scheme 4, using the compound obtained in Preparation Examp1e 13 as a starting materia1 (4 % yie1d). 1H-NMR (CDC13, 400MHz) 89.93(d, 1H), 88.82(s, 1H), 86.59(s, 1H), 55.60(d, 2H), 83.60(m, 1H), 83.42(s, 3H), 52.46(s, 3H), 82.13(d, 2H), 81.80(d, 2H), 81.20(m, 4H), 81.12(m, 1H), 81.09(s, 9H) Example     50:     Synthesis     of     2-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert- butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole The tit1e compound, which is a regioisomer, was purified through co1umn chromatography in the same manner as in Reaction Scheme 4, using the compound obtained in Preparation Examp1e 13 as a starting materia1 (38% yie1d). 1H-NMR (CDC13, 400MHz) 89.91(d, 1H), 88.61(s, 1H), 86.46(s, 1H), 85.81(s, 2H), 83.58(m, 1H), 83.45(s, 3H), 82.43(s, 3H), 82.11(d, 2H), 81.80(d, 2H), 81.21(m, 4H), 81.12(m, 1H), 81.10(s, 9H) [Reaction Scheme 5] -Rt Triphosgene, TEA Dichloromethane (0.09M) was added to each pyridin-2-amine intermediate (1 eq). Triethylamine (1.5 eq) was added to the solution, and a triphosgene dichloromethane solution (1.5 eq) was added dropwise at room temperature for 10 minutes. Each amine (1.1 eq) and triethylamine (1.5 eq) were added to the reaction solution, and the mixture was stirred at room temperature for 30 minutes. The reaction of the mixture was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with dichloromethane. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the target compound. Example 51:   Synthesis of   1-({2-[3-(4,4-dimethylcyclohexyl)-1-methylureido]-4- pyridyl}methyl)-1H-tetrazole The title compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Example 1 and 4,4-dimethylcyclohexan-1-amine as starting materials ( 0% yield). 1H-NMR (CDC13, 400MHz) 89.96(s, 1H), 88.66(s, 1H), 88.28(s, 1H), 86.86(s, 1H), 86.73(d, 1H), 85.62(s, 2H), 83.75(m, 1H), 83.36(s, 3H), 81.81(m, 2H), 81.50(m, 4H), 81.42(m, 2H), 81.31(m, 6H) Example 52: Synthesis of 3-[cyclopropyl(phenyl)methyl]-1-methyl-1-[4-(tetrazol-1- ylmethyl)-2-pyridyl]urea The title compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Example 1 and 1-cyclopropyl-1-phenylmethylamine hydrochloride as starting materials (90% yield). 1H-NMR (CDC13, 400MHz) 810.63(d, 1H), 88.67(s, 1H), 88.32(d, 1H), 87.39(d, 2H), 87.32(t, 2H), 87.25-7.22(m, 1H), 86.85(s, 1H), 86.75(d, 1H), 85.61(s, 2H), 84.50(t, 1H), 83.35(s, 3H), 81.26-1.21(m, 1H), 80.60-0.55(m, 2H), 80.49-0.39(m, 2H) Example 53: Synthesis of 3-[(R)-cyclopropyl-(2-fluorophenyl)methyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 1 and (R)-cyc1opropy1(2-f1uoropheny1)methanamine hydroch1oride as starting materia1s ( 4% yie1d). 1H-NMR (CDC13, 400MHz) 810. 8(d, 1H), 88.6 (s, 1H), 88.36(s, 1H), 8 .31(t, 1H), 8 .22- .01(m, 1H), 86.85(s, 1H), 85.62(s, 2H), 84.63(t, 1H), 83.33(s, 3H), 81.36-1.31(m, 1H), 80.62-0.56(m, 1H), 80.50-0.4 (m, 2H), 80.40-0.3 (m, 1H) Example 54: Synthesis of 3-indan-2-yl-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2- pyridyl]urea The title compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Example 1 and indan-2-amine hydrochloride as starting materials (83% yield). 1H-NMR (CDC13, 400MHz) 510.25(d, 1H), 88.65(s, 1H), 88.16(d, 1H), 87.26-7.16(m, 4H), 86.84(s, 1H), 86.71(d, 1H), 85.61(s, 2H), 84.74-4.69(m, 1H), 83.41-3.35(m, 5H), 82.92(dd, 2H) Example 55: Synthesis of 3-indan-1-yl-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 1 and indan-1-amine as starting materia1s ( 6% yie1d). 1H-NMR (CDC13, 400MHz) 810.33(d, 1H), 88.6 (s, 1H), 88.1 (d, 1H), 8 .35(d, 1H), 8 .23- .21(m, 1H), 86.88(s, 1H), 86. 2(d, 1H), 85.62(s, 2H), 83.43(s, 3H), 83.00-2.9 (m, 1H), 82.91-2.89(m, 1H), 82. 1-2.6 (m, 1H), 81.92-1.84(m, 1H) Example 56:   Synthesis of   1-methyl-3-tetralin-1-yl-1-[4-(tetrazol-1-ylmethyl)-2- pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 1 and tetra1in-1-amine hydroch1oride as starting materia1s (8 % yie1d). 1H-NMR (CDC13, 400MHz) 810.28(d, 1H), 88.65(s, 1H), 88.15(d, 1H), 8 .39(d, 1H), 8 .1 - .10(m, 3H), 86.8 (s, 1H), 86.69(d, 1H), 85.61(s, 2H), 85.20-5.18(m, 1H), 83.43(s, 3H), 82.86-2. 9(m, 2H), 82.16-2.13(m, 1H), 81.91-1.83(m, 3H) Example 57: Synthesis of 3-(2,2-dimethylchroman-4-yl)-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea The title compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Example 1 and 2,2-dimethylchroman-4-amine as starting materials (83% yield). 1H-NMR (CDC13, 400MHz) 510.43(d, 1H), 58.66(s, 1H), 58.1 7(d, 1H), 57.35(d, 1H), 57.16(t, 1H), 56.88-6.81(m, 3H), 56.74(d, 1H), 55.63(s, 2H), 55.32-5.26(m, 1H), 53.44(s, 3H), 52.31(dd, 1H), 51.86-1.80(m, 1H), 51.44(s, 3H), 51.3 (s, 3H) Example 58: Synthesis of 3-[(1R)-1-cyclohexylethyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)- 2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 1 and (1R)-1-cyc1ohexy1ethan-1-amine as starting materia1s (82% yie1d). 1H-NMR (CDC13, 400MHz) 59.9 (d, 1H), 58.65(s, 1H), 58.2 (d, 1H), 56.85(s, 1H), 56. 3(d, 1H), 55.62(s, 2H), 53.88-3.85(m, 1H), 53.3 (s, 3H), 51.82-1.60(m, 5H), 51.4 -1.45(m, 1), 51.26-0.9 (m, 8H) Example 59: Synthesis of 3-[(1,4-dimethylcyclohexyl)methyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea The title compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Example 1 and 1-(1-methylcyclohexyl)methanamine as starting materials (41% yield). 1H-NMR (CDC13, 400MHz) 810.20(s, 1H), 88.78(s, 1H), S8.2 7(d, 1H), 86.89(s, 1H), 86.77(d, 1H), 85.67(s, 2H), 83.37(s, 3H), 83.23(d, 2H), 81.49-1.39(m, 5H), 81.35-1.26(m, 5H), 80.93(s, 3H) Example 60: Synthesis of  2-[(1r,4r)-4-(3-methyl-3-{4-[(2H-tetrazol-2-yl)methyl]-2- pyridyl}ureido)cyclohexyl]-2-propanol The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 2 and 2-[(1r,4r)-4-aminocyc1ohexy1]propan-2-o1 as starting materia1s (51% yie1d). 1H-NMR (CDC13, 400MHz) 89.92(d, 1H), 88.58(s, 1H), 88.23(d, 1H), 86.89(s, 1H), 86.82(d, 1H), 85.81(s, 2H), 83.64(m, 1H), 83.3 (s, 3H), 82.14(d, 2H), 81.8 (d, 2H), 81.26(m, 5H), 81.20(s, 6H) Example     61: Synthesis      of      2-[(2-{1-methyl-3-[(1r,4r)-4-(1-fluoro-1- methylethyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole Dich1oromethane (0.3M) was added to the compound obtained in Examp1e 60 (1 eq), and the mixture was cooled to - 8°C. 1,8-Diazabicycloundec- -ene (1.5 eq) and XtalFluor-E (1.5 eq) were added to the solution, and the mixture was warmed to room temperature. The reaction solution was stirred at room temperature for 12 hours. The reaction of the mixture was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the title compound (9% yield). 1H-NMR (CDC13, 400MHz) 59.95(d, 1H), 38.58(s, 1H), 58.23(d, 1H), 36.89(s, 1H), 36.82(d, 1H), 35.81(s, 2H), 33.65(m, 1H), 33.3 7(s, 3H), 32.14(s, 2H), 31.84(d, 2H), 31.63(s, 1H), 31.52(m, 3H), 31.33(s, 3H), 31.22(m, 4H) Example 62: Synthesis of 3-[(R)-cyclopropyl-(2-fluorophenyl)methyl]-1-methyl-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea N~n  r^N 0 V 4 N 11 A A । H X J The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 2 and (R)-cyc1opropy1(2-f1uoropheny1)methanamine hydroch1oride as starting materia1s ( 8% yie1d). 1H-NMR (CDC13, 400MHz) 310.89(d, 1H), 38.58(s, 1H), 38.33(d, 1H), 3 .33- .28(m, 1H), 3 .22- .18(m, 1H), 3 .09- .00(m, 2H), 36.90(s, 1H), 36.8 (d, 1H), 35.82(s, 2H), 34.64(t, 1H), 33.34(s, 3H), 31.34-1.30(m, 1H), 30.59-0.56(m, 1H), 30.50-0.4 (m, 2H), 30.39-0.36(m, 1H) Example 63: Synthesis of 1-methyl-3-[(1S)-tetralin-1-yl]-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 2 and (1S)-tetra1in-1-amine as starting materials (85% yield). 1H-NMR (CDC13, 400MHz) 610.40(d, 1H), 68.57(s, 1H), 68.12(d, 1H), 87.39(d, 1H), 66.82(d, 1H), 67.17-7.09(m, 3H), 66.91(s, 1H), 66.79(d, 1H), 65.80(s, 2H), 65.21-5.18(m, 1H), 63.43(s, 3H), 62.85-2. 6(m, 2H), 62.16-2.13(m, 1H), 61.90-1.83(m, 3H) Example 64: Synthesis of 1-methyl-3-[(1R)-tetralin-1-yl]-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 2 and (1R)-tetra1in-1-amine as starting materia1s ( 2% yie1d). 1H-NMR (CDC13, 400MHz) 610.40(d, 1H), 68.5 (s, 1H), 68.12(d, 1H), 6 .39(d, 1H), 66.82(d, 1H), 6 .18- .09(m, 3H), 66.91(s, 1H), 66. 9(d, 1H), 65.80(s, 2H), 65.21-5.18(m, 1H), 63.43(s, 3H), 62.85-2. 6(m, 2H), 62.18-2.13(m, 1H), 61.90-1.83(m, 3H) [Reaction Scheme 6] Ru Ru = hydrogen, ethyl Rv = trifluoromethoxy, isopropyl Each amine intermediate (1 eq) was disso1ved in tetrahydrofuran (0.3M), and each isocyanate (2 eq) was added. The reaction so1ution was stirred at room temperature for 12 hours, and the reaction was quenched with water. Then, the reaction so1ution was extracted with ethy1 acetate. The resu1tant was concentrated under reduced pressure and then purified by co1umn chromatography to obtain the target compound. Example 65: Synthesis of 1-ethyl-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea The title compound was obtained in the same manner as in Reaction Scheme 6, using the compound obtained in Preparation Example 6 and 1-isocyanato-4-(trifluoromethoxy)benzene as starting materials (50% yield). 1H-NMR (CDC13, 400MHz) 512.7 7(s, 1H), 58.60(s, 1H), 58.34(d, 1H), 57.58(d, 2H), 5 7.18(d, 2H), 56.98(s, 1H), 56.92(d, 1H), 55.86(s, 2H), 54.05(q, 2H), 51.31(t, 3H) Example 66: Synthesis of 1-(4-isopropylphenyl)-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 6, using the compound obtained in Preparation Examp1e 1 and 1-isocyanato-4-isopropy1-benzene as starting materia1s (54% yie1d). 1H-NMR (CDC13, 400MHz) 5ddd(s, 1H), 58.5 (s, 1H), 58.2 (d, 1H), 5 .55(s, 1H), 5 .48(d, 2H), 5 .22(d, 2H), 56.84(d, 1H), 56. 0(s, 1H), 55. 9(s, 2H), 52.91(m, 1H), 51.25(d, 6H) Example 67: Synthesis of 1-[(6-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-2- pyridyl)methyl]-1H-tetrazole The compound obtained in Preparation Examp1e 19 (1 eq), 1H-1,2,3,4-tetrazo1e (4 eq) and potassium carbonate (2 eq) were added to acetonitrile (0.1M) and stirred at 90°C for 12 hours. The reaction solution was cooled to room temperature and filtered to remove potassium carbonate. The filtrate was dried, diluted with saturated aqueous sodium chloride solution, and then extracted with ethyl acetate. The resultant was concentrated under reduced pressure and then purified by column chromatography to obtain the title compound (2 % yield). 1H-NMR (CDC13, 400MHz) 68.65(s, 1H), 88.44(s, 1H), 67.63(t, 1H), 66.86-6.78(m, 2H), 65.61(s, 2H), 63.67-3.59(m, 1H), 62.07(d, 2H), 61.85(d, 2H), 61.25-1.08(m, 5H), 60.87(s, 9H) Example 68: Synthesis of 2-[(6-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-2- pyridyl)methyl]-2H-tetrazole The tit1e compound, which is a regioisomer, was purified through co1umn chromatography in the same manner as in Examp1e 6 , using the compound obtained in Preparation Examp1e 19 as a starting materia1 (24% yie1d). 1H-NMR (CDC13, 400MHz) 68. 8(s, 1H), 68.56(s, 1H), 6 .60(t, 1H), 66.89(d, 1H), 66. 0(d, 1H), 65.81(s, 2H), 63.68-3.60(m, 1H), 62.0 (d, 2H), 61.86(d, 2H), 61.34-1.25(m, 2H), 61.20-1.04(m, 3H), 60.88(s, 9H) Example 69: Synthesis of 1-(1-adamantyl)-3-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Preparation Examp1e 1 , using the compound obtained in Preparation Examp1e 20 as a starting materia1. 1H-NMR (DMSO-d6, 400MHz) 69.55(s, 1H), 68.98(s, 1H), 68.14(d, 1H), 6 .63(s, 1H), 6 .32(s, 1H), 66. 5(d, 2H), 65. 5(s, 2H), 62.03(s, 3H), 61.95(s, 6H), 61.64(s, 6H) Example 70: Synthesis of 1-(1-adamantyl)-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Example 69, using the compound obtained in Preparation Example 20 as a starting material. 1H-NMR (CDC13, 400MHz) 39.07(s, 1H), 88.99(s, 1H), 58.15(d, 1H), 57.64(s, 1H), 57.34(s, 1H), 56.76(d, 1H), 55.99(s, 2H), 82.03(s, 3H), 51.95(s, 6H), 51.64(s, 6H) Example 71: Synthesis of 3-methyl-1-[(1r,4r)-4-tert-butylcyclohexyl]-3-{4-[2-(2H-1,2,3,4- tetrazol-2-yl)ethyl]pyridin-2-yl}urea The compound obtained in Preparation Examp1e 21 (1 eq) was disso1ved in dich1oromethane (0.3M), and thiony1 ch1oride (4 eq) was added. The reaction so1ution was stirred at room temperature for 12 hours. Then, the reaction was quenched with saturated aqueous sodium bicarbonate so1ution, and the mixture was extracted with dich1oromethane. The so1ution was concentrated under reduced pressure and disso1ved in DMF (0.3M), and then cesium carbonate (1.5 eq) and 1H-1,2,3,4-tetrazo1e (1.5 eq) were added. The reaction so1ution was stirred at 0°C for 12 hours, quenched with water, and then extracted with dich1oromethane. The resu1tant was concentrated under reduced pressure and then purified by co1umn chromatography to obtain the tit1e compound (25% yie1d). 1H-NMR (CDC13, 400MHz) 59.97(d, 1H), 58.50(s, 1H), 58.14(d, 1H), 56.71(d, 2H), 54.95(t, 2H), 53.63(m, 1H), 53.35(m, 5H), 52.13(d, 2H), 51.81(d, 2H), 51.21(m, 5H), 51.00(m, 1H), 50.85(s, 9H) Example 72: Synthesis of 3-methyl-1-[(1r,4r)-4-tert-butylcyclohexyl]-3-{4-[2-(1H-1,2,3,4- tetrazol-1-yl)ethyl]pyridin-2-yl}urea The title compound, which is a regioisomer, was purified through column chromatography in the same manner as in Example 1, using the compound obtained in Preparation Example 21 as a starting material (19% yield). 1H-NMR (CDC13, 400MHz) 39.86(d, 1H), 58.36(s, 1H), 38.16(d, 1H), 56.65(m, 2H), 34.70(t, 2H), 33.64(m, 1H), 53.32(m, 5H), 32.11(d, 2H), 31.81(d, 2H), 31.19(m, 6H), 31.00(m, 1H), 30.86(s, 9H) Example     73:     Synthesis     of     methyl     2-[1-[[[4-(tetrazol-2-ylmethyl)-2- pyridyl]carbamoylamino]methyl]cyclohexyl]acetate The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 1 and methy1 2-[1-(aminomethy1)cyc1ohexy1]acetate as starting materia1s. 1H-NMR (CDC13, 400MHz) 38.60 (s, 1H), 38.15(m, 1H), 36.78 (s, 1H), 35.81(s, 2H), 33.70(m, 3H), 33.43(d, 2H), 32.39(s, 2H), 31.50-1.47(m, 9H) Example 74: Synthesis of 1-[(2R,4R)-norbornan-2-yl]-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Example 1 and (2R,4R)-norbornan-2-amine as starting materials. 1H-NMR (CDC13, 400MHz) 58.64 (s, 1H), 58.06(br, 1H), 56.83(m, 1H), 55.90(m, 2H), 54.11(m, 1H), 52.46(s, 1H), 52.27(s, 1H) 52.12(m, 1H), 51.66-1.27(m, 6H), 50.97-0.86(m, 2H) Example 75: Synthesis of 1-[1-(1-adamantyl)ethyl]-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea The tit1e compound was obtained in the same manner as in Reaction Scheme 5, using the compound obtained in Preparation Examp1e 1 and 1-(1-adamanty1)ethanamine as starting materia1s. 1H-NMR (DMSO-d6, 400MHz) 59.15(s, 1H), 59.08(s, 1H) 58.1 (s, 1H), 5 .82(br 1H), 5 .294(s, 1H), 56. 8(s, 1H), 56.00(s, 2H), 53.42(m 1H) 51.95(m, 4H), 51.6 -1.45(m, 11H), 50.99-0.9 (m, 3H) Experimental Example: Pharmacological Activity Test The efficacy of the compounds of the Examp1es as g1ucocerebrosidase activators was tested as fo11ows. Cell-free assay using imiglucerase 484 pL of phosphatidylserine (Avanti Polar Lipids, Inc Cat. No. SKU840032C) dissolved in a 1mg / ml chloroform solution was aliquoted and evaporated with a stream of nitrogen for 1 hour. 40 ml of 50 mM citric acid / 1 6 mM potassium phosphate (pH4. ) and .5 pL of triton X-100 were added thereto and mixed for 5 minutes (vortexing) to prepare mixed micelles of 0.32 mM triton and 0.3 mol% phosphatidylserine. 0.4 pL of a 5 mM test compound was dispensed into a 96 well plate, and 100 pL of imiglucerase (donated by ISU ABXIS) 50 nM / saposin C (Sapocin C, EnzoLifescience, ALX-201-262) dissolved in 1 pM of 0.32 mM Triton / 0.3 mol% reaction buffer solvent was added to the well and reacted at room temperature for 30 minutes. 25 pL of this reaction product was aliquoted, mixed with 25 uL of 4mM 4-methylumbelliferyl-beta-D-glucopyranoside (4-MU, Sigma-Aldrich M3633), and reacted at room temperature for 15 minutes. After 15 minutes, the reaction was terminated with 150 uL of a stop solution of 1M glycine pH 12.5, and then the fluorescence intensity (excitation: 365 nm, emission: 440 nm) was measured with a SpectraMax M4 or Flitermax (Molecular Devices) instrument to confirm the reaction. Measurement of glucocerebrosidase activity in fibroblasts Fibroblasts were seeded in a 96-well cell culture plate at 10,000 cells per well and cultured for 1 day at 37OC and 5% CO2 in a culture medium of DMEM (Gibco) with 15% FBS and penicillin / streptomycin. Thereafter, on the next day, the test compound was added to the cells, and after culturing for 3 days, the compound was treated again while replacing the culture medium on day 5. On day 7 of cell culture, the cultured cells were washed with 100 pL of 3 7OC PBS, and then 20 pL of 0.2M sodium acetate pH 4.0 buffer solution, 2 pL of 3 7OC PBS and 25 pL of 4-MU solution were added to each well, and the cells were incubated in a 3 7°C carbon dioxide incubator for 1 hour. 150 pL of 0.2M glycine pH 12 buffer solution per well was added as a stop solution and left in a 3 7OC carbon dioxide incubator for 5 minutes, and then the fluorescence intensity (excitation: 365 nm, emission: 440 nm) was measured with a SpectraMax M4 or Filtermax (Molecular Devices) to confirm the reaction. Results The measured degree of glucocerebrosidase activation is shown in Table 1 below. These are the results of testing at 10 pM in each of the cell-free test and the cell test, and are indicated according to the following criteria. ++++: activation of more than 90% +++: activation of more than 60%-90% ++: activation of more than 30%-60% +: activation of 30% or less ND (not determined): not measured [Table 1] Compound Cell-free assay activity (%) Cell assay activity (%) Example 1 ++++ +++ Example 2 +++ ++ Example 3 ++++ +++ Example 4 ++++ +++ Example 5 ++++ ++ Example 6 + + Example 7 ++ + Example 8 ++++ ++ Example 9 ++ + Example 10 +++ + Example 11 ++ + Example 12 +++ +++ Example 13 +++ +++ Example 14 ++++ ++ Example 15 ++++ + Example 16 ++++ ++ Example 17 +++ ++ Example 18 ++ ++ Example 19 ++ ++ Example 20 + +++ Example 21 + ++ Example 22 ++++ +++ Example 23 +++ ++ Example 24 ++++ ++ Example 25 +++ + Example 26 ++++ ++++ Example 2 7 ++++ ++++ Example 28 ++++ ++ Example 29 ++++ ++ Example 30 ++++ ++ Example 31 ND ++ Example 32 + + Example 33 ++ +++ Example 34 ++ ++ Example 35 +++ +++ Example 36 + + Example 37 ++++ + Example 38 ++ ++ Example 39 ++ + Example 40 +++ ++ Example 41 +++ + Example 42 ++ +++ Example 43 ++ ++ Example 44 ND + Example 45 ++++ +++ Example 46 ++++ ++++ Example 4 7 ++++ +++ Example 48 ++++ ++++ Example 49 ++++ +++ Example 50 ++++ ++++ Example 51 +++ + Example 52 +++ + Example 53 ++++ + Example 54 ++ + Example 55 ++ + Example 56 +++ ++ Example 5 7 ++ + Example 58 +++ + Example 59 +++ + Example 60 + + Example 61 ++ + Example 62 ++++ ++ Example 63 +++ + Example 64 +++ ++ Example 65 ++ + Example 66 ++ ++ Example 6 7 ++++ +++ Example 68 ++++ ++ Example 69 ++++ ++ Example 7 0 ND ++ Example 71 ++++ +++ Example 7 2 ++++ +++ Example 73 ND + Example 74 ND + Example 75 ND ++

Claims

1. A compound of the following Formula 1, or a pharmaceutically acceptable salt orstereoisomer thereof:[Formula 1]wherein, in Formula 1,X is N or CH;R1 and R3 are each independently -H, halo, alkyl or; wherein R is, and m is 1 or 2; wherein R8 is -H, alkyl, hydroxyalkyl,haloalkyl, dialkylaminocarbonyloxyalkyl or aryl;R2 is -H, halo or alkyl;R4 is -H or alkyl;R5 is -H, alkyl or cycloalkyl;R6 is saturated or partially unsaturated carbocyclyl, aryl or partially unsaturated heterocyclyl; wherein the saturated or partially unsaturated carbocyclyl and aryl may be optionally substituted with one or more substituents selected from the group consisting of halo, alkyl, hydroxyalkyl, haloalkyl, haloalkoxy, cycloalkyl and alkoxycarbonylalkyl;n is 0 or 1; andthe partially unsaturated heterocyclyl may contain one or more heteroatoms selected from N, O and S,provided that at least one of R1 and R3 is2.The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, whereinX is N or CH;R1 and R3 are each independently -H, halo, C1-C alkyl or; wherein R 7isor, and m is 1 or 2; wherein R8 is -H, C1-C alkyl, hydroxy-C1-C alkyl, halo-C1-C alkyl, di(C1-C alkyl)aminocarbonyloxy-C1-C alkyl or C6-C10 aryl;R2 is -H, halo or C1-C alkyl;R4 is -H or C1-C alkyl;R5 is -H, C1-C alkyl or C3-C10 cycloalkyl;R6 is saturated or partially unsaturated C5-C12 carbocyclyl, C6-C10 aryl or partially unsaturated 5- to 12-membered heterocyclyl; wherein the saturated or partially unsaturated carbocyclyl and aryl may be optionally substituted with 1 to 3 substituents selected from the group consisting of halo, C1-C alkyl, hydroxy-C1-C alkyl, halo-C1-C alkyl, halo-C1-C alkoxy, C3-C10 cycloalkyl and C1-C alkoxycarbonyl-C1-C alkyl;n is 0 or 1; andthe partially unsaturated heterocyclyl may contain 1 to 3 heteroatoms selected from N,O and S,provided that at least one of R1 and R3 is3.      The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, whereinR1 is -H or; wherein R isor, and m is1 or 2; wherein R8 is -H, C1-C5 alkyl, hydroxy-C1-C5 alkyl, halo-C1-C5 alkyl, di(C1-C5alkyl)aminocarbonyloxy-C1-C5 alkyl or phenyl; andR3 is -H, C1-C5 alkyl or; wherein R isor, and m is 1 or 2; wherein R8 is -H or C1-C5 alkyl,provided that at least one of R1 and R3 is4.      The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, wherein R2 is -H, halo or C1-C5 alkyl.

5. The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, wherein R4 is -H or C1-C5 alkyl.

6. The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, wherein R5 is -H, C1-C5 alkyl or C3-C8 cycloalkyl..      The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, wherein R6 is saturated or partially unsaturated C6-C12 carbocyclyl, phenyl or partially unsaturated 8- to 12-membered heterocyclyl, wherein the saturated or partially unsaturated carbocyclyl may be optionally substituted with 1 to 3 substituents selected from the group consisting of halo, C1-C alkyl, hydroxy-C1-C alkyl, halo-C1-C alkyl and C1-C alkoxycarbonyl-C1-C alkyl; and the phenyl may be optionally substituted with 1 to 3 substituents selected from the group consisting of halo, C1-C alkyl, halo-C1-C alkyl, halo-C1-C alkoxy and C3-C10 cycloalkyl.

8. The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim , wherein R6 is saturated or partially unsaturated C6-C12 carbocyclyl, or partially unsaturated 8- to 12-membered heterocyclyl, wherein the saturated or partially unsaturated carbocyclyl may be optionally substituted with 1 to 3 substituents selected from the group consisting of halo, C1-C alkyl, hydroxy-C1-C alkyl, halo-C1-C alkyl and C1-C alkoxycarbonyl-C1-C alkyl.

9. The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 8, wherein the saturated or partially unsaturated C6-C12 carbocyclyl, or partially unsaturated 8- to 12-membered heterocyclyl of R6 is cyclohexyl, spiro[2.5]octyl, spiro[3.5]nonyl, adamantyl, norbornanyl, indanyl, tetralinyl or chromanyl.

10. The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, wherein the compound of Formula 1 is selected from the group consisting of:1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 1);1-[(2-{1-ethyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 2);1-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 3);2-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 4);2-[(2-{1-methyl-3-[(1s,4s)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 5);1-({2-[3-(4,4-difluorocyclohexyl)-1-methylureido]-4-pyridyl}methyl)-1H-tetrazole (Compound 6);2-[(2-{1-methyl-3-[(1r,4r)-4-(trifluoromethyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound );2-[(2-{1-methyl-3-[(1r,4r)-4-isopropylcyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 8);1-[(2-{1-methyl-3-(6-spiro[2.5]octyl)ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 9);1-[(2-{1-methyl-3-( -spiro[3.5]nonyl)ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 10);1-methyl-3-[(4-methylcyclohexyl)methyl]-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 11);2-[(2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 14);1-[(2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 15);5-methyl-2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 16);5-methyl-1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 1 );2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-propyl-2H-tetrazole (Compound 18);1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-propyl-1H-tetrazole (Compound 19);2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-(trifluoromethyl)-2H-tetrazole (Compound 20);1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-5-(trifluoromethyl)-1H-tetrazole (Compound 21);2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 22);{1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazol-5-yl}methanol (Compound 23);{2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazol-5-yl}methanol (Compound 24);[2-({2-[methyl({[(1r,4r)-4-tert-butylcyclohexyl]carbamoyl})amino]pyridin-4-yl}methyl)-2H-1,2,3,4-tetrazol-5-yl]methyl N,N-dimethylcarbamate (Compound 25);1-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 26);2-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 2 );2-[(5-fluoro-2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 28);1-[(5-fluoro-2-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyridyl)methyl]-1H-tetrazole (Compound 29);1-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-1H-tetrazole (Compound 45);2-[(2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole (Compound 46);1-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-1H-tetrazole (Compound 4 );2-[(5-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole (Compound 48);1-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-1H-tetrazole (Compound 49);2-[(6-methyl-2-{1-methyl-3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-4-pyrimidinyl)methyl]-2H-tetrazole (Compound 50);1-({2-[3-(4,4-dimethylcyclohexyl)-1-methylureido]-4-pyridyl}methyl)-1H-tetrazole (Compound 51);3-[(1R)-1-cyclohexylethyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 58);3-[(1,4-dimethylcyclohexyl)methyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 59);2-[(1r,4r)-4-(3-methyl-3-{4-[(2H-tetrazol-2-yl)methyl]-2-pyridyl}ureido)cyclohexyl]-2-propanol (Compound 60);2-[(2-{1-methyl-3-[(1r,4r)-4-(1-fluoro-1-methylethyl)cyclohexyl]ureido}-4-pyridyl)methyl]-2H-tetrazole (Compound 61);1-[(6-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-2-pyridyl)methyl]-1H-tetrazole (Compound 6 );2-[(6-{3-[(1r,4r)-4-(tert-butyl)cyclohexyl]ureido}-2-pyridyl)methyl]-2H-tetrazole (Compound 68);1-(1-adamantyl)-3-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 69);1-(1-adamantyl)-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 0);3-methyl-1-[(1r,4r)-4-tert-butylcyclohexyl]-3-{4-[2-(2H-1,2,3,4-tetrazol-2-yl)ethyl]pyridin-2-yl}urea (Compound 1);3-methyl-1-[(1r,4r)-4-tert-butylcyclohexyl]-3-{4-[2-(1H-1,2,3,4-tetrazol-1-yl)ethyl]pyridin-2-yl}urea (Compound 2);methyl                                              2-[1-[[[4-(tetrazol-2-ylmethyl)-2-pyridyl]carbamoylamino]methyl]cyclohexyl]acetate (Compound 3);1-[(2R,4R)-norbornan-2-yl]-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 4); and1-[1-(1-adamantyl)ethyl]-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 5).

11. The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, wherein the compound of Formula 1 is selected from the group consisting of:3-(4-cyclopropylphenyl)-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 12);1-methyl-3-(4-propylphenyl)-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea   (Compound13);1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 30);1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 31);1-[4-[(5-methyltetrazol-1-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 32);1-[4-[(5-methyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 33);1-[4-[[5-(hydroxymethyl)tetrazol-1-yl]methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 34);1-[4-[[5-(hydroxymethyl)tetrazol-2-yl]methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 35);1-[6-methyl-4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 36);1-[6-methyl-4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 3 );1-[6-methyl-4-[(5-methyltetrazol-1-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 38);1-[6-methyl-4-[(5-methyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 39);1-[4-[[5-(hydroxymethyl)tetrazol-1-yl]methyl]-6-methyl-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 40);1-[4-[[5-(hydroxymethyl)tetrazol-2-yl]methyl]-6-methyl-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 41);1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 42);1-methyl-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 43);1-[4-[(5-phenyltetrazol-2-yl)methyl]-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 44);3-[cyclopropyl(phenyl)methyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 52);3-[(R)-cyclopropyl-(2-fluorophenyl)methyl]-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 53);3-[(R)-cyclopropyl-(2-fluorophenyl)methyl]-1-methyl-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 62);1-ethyl-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]-3-[4-(trifluoromethoxy)phenyl]urea (Compound 65); and1-(4-isopropylphenyl)-3-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 66).

12. The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, wherein the compound of Formula 1 is selected from the group consisting of:3-indan-2-yl-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 54);3-indan-1-yl-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 55);1-methyl-3-tetralin-1-yl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea (Compound 56);3-(2,2-dimethylchroman-4-yl)-1-methyl-1-[4-(tetrazol-1-ylmethyl)-2-pyridyl]urea(Compound 5 );1-methyl-3-[(1S)-tetralin-1-yl]-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 63); and1-methyl-3-[(1R)-tetralin-1-yl]-1-[4-(tetrazol-2-ylmethyl)-2-pyridyl]urea (Compound 64).

13. The compound, or a pharmaceutically acceptable salt or stereoisomer thereof,according to claim 1, wherein the pharmaceutically acceptable salt is nitrate, sulfate, hydrobromide, toluenesulfonate, hydrochloride, methanesulfonate or camphorsulfonate.

14. A pharmaceutical composition for the prevention or treatment of a disease mediatedby P-glucocerebrosidase, comprising, as an active ingredient, the compound of Formula 1 as defined in any one of claims 1 to 13, or a pharmaceutically acceptable salt or stereoisomer thereof, together with a pharmaceutically acceptable carrier.

15. The pharmaceutical composition according to claim 14, wherein the disease mediatedby P-glucocerebrosidase is Parkinson's disease, Gaucher's disease, Lewy body dementia or synucleinopathy.